Joseph F Urban

United States Department of Agriculture, Washington, Washington, D.C., United States

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Publications (225)1648.76 Total impact

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    ABSTRACT: IL-25 or IL-17E is a member of IL-17 cytokine family and has immune-modulating activities. The role of IL-25 in maintaining lipid metabolic homeostasis remains unknown. We investigated the effects of exogenous IL-25 or deficiency of IL-25 on hepatic lipid accumulation. IL-25 expression was examined in paraffin-embedded tissue sections of liver from patients or in the livers from mice. Mouse model of steatosis was induced by feeding a high-fat diet (HFD). Extent of steatosis as well as expression of cytokines, key enzymes for lipid metabolic pathways, markers for Kupffer cells/macrophages, and lipid droplet (LD) proteins, were analyzed. Our results show that hepatic steatosis in mice was accompanied by increased LD proteins, but decreased IL-25 in the liver. Decreased hepatic IL-25 was also observed in patients with fatty liver. Administration of IL-25 to HFD-fed wild-type mice led to a significant improvement in hepatic steatosis. This effect was associated with increased expression of IL-13, development of alternatively activated Kupffer cells/macrophages, and decreased expression of LD proteins in the liver. In contrast, administration of IL-25 to HFD-fed mice deficient in STAT6 or IL-13 had no effects. In addition, stimulation of primary hepatocytes with IL-13, but not IL-25, resulted in downregulation of LD proteins. Finally, mice deficient in IL-25 had exacerbated hepatic lipid accumulation when fed the HFD. These data demonstrate that dysregulated IL-25 expression contributes to lipid accumulation, whereas exogenous IL-25 protects against hepatic steatosis through IL-13 activation of STAT6. IL-25 and IL-13 are potential therapeutic agents for hepatic steatosis and associated pathologies.
    The Journal of Immunology 10/2015; DOI:10.4049/jimmunol.1500337 · 4.92 Impact Factor
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    ABSTRACT: Background: Dynamic interactions between the host and gastrointestinal microbiota play an important role for local and systemic immune homeostasis. Helminthic parasites modulate the host immune response, resulting in protection against autoimmune disease but also increased susceptibility to pathogen infection. The underlying mechanisms remain largely unknown. Results: We showed that the type 2 immune response to enteric Nippostrongylus brasiliensis infection in mice was associated with altered intestinal mucin and AMP expression and shifts in microbiota composition. Most strikingly, infection reduced concentrations of intestinal segmented filamentous bacteria (SFB), known inducers of T helper 17 cells, and IL-17-associated gene expression. Infected mice deficient in IL-13 or STAT6 did not reduce SFB or IL-17, and exogenous IL-25 replicated the effects of parasite infection in wild type mice. Conclusions: Our data show that parasite infection acts through host type 2 immunity to reduce intestinal SFB and expression of IL-17, providing an example of a microbiota-dependent immune modulation by parasites.
    09/2015; 3(1):40. DOI:10.1186/s40168-015-0103-8
  • Liying Guo · Yuefeng Huang · Xi Chen · Jane Hu-Li · Joseph F Urban · William E Paul ·
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    ABSTRACT: Type 2 helper T cells (TH2 cells) produce interleukin 13 (IL-13) when stimulated by papain or house dust mite extract (HDM) and induce eosinophilic inflammation. This innate response is dependent on IL-33 but not T cell antigen receptors (TCRs). While type 2 innate lymphoid cells (ILC2 cells) are the dominant innate producers of IL-13 in naive mice, we found here that helminth-infected mice had more TH2 cells compared to uninfected mice, and thes e cells became major mediators of innate type 2 responses. TH2 cells made important contributions to HDM-induced antigen-nonspecific eosinophilic inflammation and protected mice recovering from infection with Ascaris suum against subsequent infection with the phylogenetically distant nematode Nippostrongylus brasiliensis. Our findings reveal a previously unappreciated role for effector TH2 cells during TCR-independent innate-like immune responses.
    Nature Immunology 08/2015; 16(10). DOI:10.1038/ni.3244 · 20.00 Impact Factor
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    ABSTRACT: The role of muscarinic receptors in mucosal homeostasis, response to enteric pathogens, and modulation of immune cell function is undefined. The contribution of type 3 muscarinic receptors (M3R) to mucosal homeostasis within the colon and host defense against Citrobacter rodentium was determined in uninfected and C. rodentium-infected WT and M3R-deficient (Chrm3) mice. In addition, WT and Chrm3 bone marrow-derived macrophages were studied to determine the ability of M3R to modulate macrophage phenotype and function. In Chrm3 mice, clearance of C. rodentium was delayed despite an amplified TH1/TH17 response. Delayed clearance of C. rodentium from Chrm3 mice was associated with prolonged adherence of bacteria to colonic mucosa, decreased goblet cell number, and decreased mucin 2 gene expression. Treatment of bone marrow-derived macrophages with bethanechol, a muscarinic-selective agonist, induced a classically activated macrophage phenotype, which was dependent on M3R expression. Chrm3 bone marrow-derived macrophages retained their ability to attain a classically activated macrophage phenotype when treated with the TH1 cytokine IFN-γ. In Chrm3 mice, mucin production is attenuated and is associated with prolonged adherence of C. rodentium to colonic mucosa. The immune response, as characterized by production of TH1/TH17 cytokines, in C. rodentium-infected Chrm3 mice is intact. In addition, M3R activity promotes the development of classically activated macrophages. Our data establish a role for M3R in host defense against C. rodentium through effects on goblet cell mucus production and in the modulation of macrophage phenotype and function.
    Inflammatory Bowel Diseases 05/2015; 21(8). DOI:10.1097/MIB.0000000000000408 · 4.46 Impact Factor
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    ABSTRACT: Most animals are concurrently infected with multiple parasite species and live in environments with fluctuating resource availability. Resource limitation can influence host immune responses and the degree of competition between co-infecting parasites, yet its effects on individual health and pathogen transmission have not been studied for co-infected hosts. To test how resource limitation affects immune trade-offs and co-infection outcomes, we conducted a factorial experiment using laboratory mice. Mice were given a standard or low protein diet, dosed with two species of helminths (alone and in combination), and then challenged with a microparasite. Using a community ecology trophic framework, we found that co-infection influenced parasite survival and reproduction via host immunity, but the magnitude and direction of responses depended on resources and the combination of co-infecting parasites. Our findings highlight that resources and their consequence for host defenses are a key context that shapes the magnitude and direction of parasite interactions. Copyright © 2015. Published by Elsevier Ltd.
    International journal for parasitology 03/2015; 45(7). DOI:10.1016/j.ijpara.2015.02.005 · 3.87 Impact Factor
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    ABSTRACT: Innate lymphoid cells (ILCs) are lymphocyte-like cells that lack T cell or B cell antigen receptors and mediate protective and repair functions through cytokine secretion. Among these, type 2 ILCs (ILC2 cells) are able to produce type 2 cytokines. We report the existence of an inflammatory ILC2 (iILC2) population responsive to interleukin 25 (IL-25) that complemented IL-33-responsive natural ILC2 (nILC2) cells. iILC2 cells developed into nILC2-like cells in vitro and in vivo and contributed to the expulsion of Nippostrongylus brasiliensis. They also acquired IL-17-producing ability and provided partial protection against Candida albicans. We propose that iILC2 cells are transient progenitors of ILCs mobilized by inflammation and infection that develop into nILC2-like cells or ILC3-like cells and contribute to immunity to both helminths and fungi.
    Nature Immunology 12/2014; 16(2). DOI:10.1038/ni.3078 · 20.00 Impact Factor
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    ABSTRACT: Donor T lymphocyte transfer with hematopoietic stem cells suppresses residual tumor growth (graft-versus-tumor [GVT]) in cancer patients undergoing bone marrow transplantation (BMT). However, donor T cell reactivity to host organs causes severe and potentially lethal inflammation called graft-versus-host disease (GVHD). High-dose steroids or other immunosuppressive drugs are used to treat GVHD that have limited ability to control the inflammation while incurring long-term toxicity. Novel strategies are needed to modulate GVHD, preserve GVT, and improve the outcome of BMT. Regulatory T cells (Tregs) control alloantigen-sensitized inflammation of GVHD, sustain GVT, and prevent mortality in BMT. Helminths colonizing the alimentary tract dramatically increase the Treg activity, thereby modulating intestinal or systemic inflammatory responses. These observations led us to hypothesize that helminths can regulate GVHD and maintain GVT in mice. Acute GVHD was induced in helminth (Heligmosomoides polygyrus)-infected or uninfected BALB/c recipients of C57BL/6 donor grafts. Helminth infection suppressed donor T cell inflammatory cytokine generation and reduced GVHD-related mortality, but maintained GVT. H. polygyrus colonization promoted the survival of TGF-β-generating recipient Tregs after a conditioning regimen with total body irradiation and led to a TGF-β-dependent in vivo expansion/maturation of donor Tregs after BMT. Helminths did not control GVHD when T cells unresponsive to TGF-β-mediated immune regulation were used as donor T lymphocytes. These results suggest that helminths suppress acute GVHD using Tregs and TGF-β-dependent pathways in mice. Helminthic regulation of GVHD and GVT through intestinal immune conditioning may improve the outcome of BMT. Copyright © 2014 by The American Association of Immunologists, Inc.
    The Journal of Immunology 12/2014; 194(3). DOI:10.4049/jimmunol.1303099 · 4.92 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate parasite induced immune responses in pigs co-infected with Trichuris suis and Oesophagostomum dentatum as compared to mono-species infected pigs. T. suis is known to elicit a strong immune response leading to rapid expulsion, and a strong antagonistic effect on O. dentatum populations has been observed in co-infected pigs. Forty-eight helminth naïve pigs were allocated into 4 groups in a 2-factorial design. Two groups were trickle inoculated with either 10 T. suis eggs/kg/day (Group T) or 20 O. dentatum L3/kg/day (Group O). Group OT was infected with same levels of both T. suis and O. dentatum (Group OT) and Group C remained uninfected. In each group, six pigs were necropsied after 35 days and the remaining pigs after 71 days. Parasite E/S-antigen specific serum antibodies were quantified by an in-direct ELISA. qPCR was used to measure the expression of immune function related genes in the mucosa of proximal colon and the draining lymph node. Highly significant interactions were identified for O. dentatum specific IgG1 (p<0.0001) and IgG2 (p<0.0006) antibodies with a remarkable 2-fold higher antibody response in group OT pigs as compared to group O. These findings indicated that T. suis enhanced the antibody response against O. dentatum in Group OT. The gene expression data confirmed a strong Type 2 response to T. suis (e.g. marked increase in IL-13, ARG1 and CCL11) and clearly weaker in amplitude and/or delayed onset response to O. dentatum in the single infected group. Interactions were found between the two nematodes with regard to several cytokines, e.g. the increase in IL-13 observed in Group T was absent in Group OT (p=0.06, proximal colon mucosa, 35 and 71p.i.). Some of these immune response-related interactions may support, or even partially explain, the observed interactions between the two worm populations in co-infected pigs. Copyright © 2014 Elsevier B.V. All rights reserved.
    Veterinary Parasitology 12/2014; 207(3-4). DOI:10.1016/j.vetpar.2014.12.005 · 2.46 Impact Factor
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    ABSTRACT: IL-25 is emerging as a key regulator of inflammation in the intestinal mucosa because of its ability to promote type 2 while suppressing Th1 and Th17 responses. Several previous studies reported inconsistent results on the role of exogenous IL-25 in development of colonic inflammation and none were performed in animals with a genetic deletion of IL-25. We investigated the contribution of endogenous IL-25 to DSS-induced colitis using mice deficient in IL-25. Mice were exposed to DSS in drinking water ad libitum either for seven days (acute) or for three cycles of seven days with DSS followed by 14 days without DSS (chronic) to induce colitis, respectively. The loss of body weight, appearance of diarrhea and bloody stools, and shortening of colon length were significantly less pronounced in IL-25(-/-) mice compared to WT mice after exposure to acute DSS. Histological examination showed that DSS-treated IL-25(-/-) mice had only mild inflammation in the colon, while severe inflammation developed in DSS-treated WT mice. A significant up-regulation of IL-33 was observed in acute DSS-treated WT but not in the IL-25(-/-) mice. There was significantly lower expression of pro-inflammatory cytokines in the colon of acute DSS-treated IL-25(-/-) compared to WT mice. IL-25(-/-) mice were also partially protected from chronic DSS challenge especially during the first 2 cycles of DSS exposure. In contrast to IL-25(-/-) mice, IL-13(-/-) mice were more susceptible to DSS-induced colitis. Finally, stimulation of T84 colonic epithelial cells with IL-25 up-regulated the expression of IL-33 and several pro-inflammatory cytokines. These data indicate that endogenous IL-25 acts as a pro-inflammatory factor in DSS-induced colitis, which is unlikely to be mediated by IL-13 but possibly the induction of IL-33 and other pro-inflammatory mediators from colonic epithelial cells. The present study suggests that IL-25 may contribute to the pathogenesis of inflammatory bowel disease in at least a subgroup of patients.
    Cell and Bioscience 11/2014; 4(1):72. DOI:10.1186/2045-3701-4-72 · 3.63 Impact Factor
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    ABSTRACT: We examined the role of innate cells in acquired resistance to the natural murine parasitic nematode, Nippostrongylus brasiliensis. Macrophages obtained from lungs as late as 45 d after N. brasiliensis inoculation were able to transfer accelerated parasite clearance to naive recipients. Primed macrophages adhered to larvae in vitro and triggered increased mortality of parasites. Neutrophil depletion in primed mice abrogated the protective effects of transferred macrophages and inhibited their in vitro binding to larvae. Neutrophils in parasite-infected mice showed a distinct transcriptional profile and promoted alternatively activated M2 macrophage polarization through secretory factors including IL-13. Differentially activated neutrophils in the context of a type 2 immune response therefore prime a long-lived effector macrophage phenotype that directly mediates rapid nematode damage and clearance.
    Nature Immunology 08/2014; 15(10). DOI:10.1038/ni.2984 · 20.00 Impact Factor
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    ABSTRACT: Alternative (M2) activation of macrophages driven via the α-chain of the receptor for interleukin 4 (IL-4Rα) is important for immunity to parasites, wound healing, the prevention of atherosclerosis and metabolic homeostasis. M2 polarization is dependent on fatty acid oxidation (FAO), but the source of the fatty acids that support this metabolic program has not been clear. We found that the uptake of triacylglycerol substrates via the scavenger receptor CD36 and their subsequent lipolysis by lysosomal acid lipase (LAL) was important for the engagement of elevated oxidative phosphorylation, enhanced spare respiratory capacity (SRC), prolonged survival and expression of genes that together define M2 activation. Inhibition of lipolysis suppressed M2 activation during infection with a parasitic helminth and blocked protective responses to this pathogen. Our findings delineate a critical role for cell-intrinsic lysosomal lipolysis in M2 activation.
    Nature Immunology 08/2014; 15(9). DOI:10.1038/ni.2956 · 20.00 Impact Factor

  • Gastroenterology 05/2014; 146(5):S-655. DOI:10.1016/S0016-5085(14)62383-0 · 16.72 Impact Factor
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    ABSTRACT: How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A-deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)-producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.
    Science 01/2014; 343(6169):432-7. DOI:10.1126/science.1247606 · 33.61 Impact Factor
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    ABSTRACT: Parasitic enteric nematodes induce a type 2 immune response characterized by increased production of Th2 cytokines, IL-4 and IL-13, and recruitment of alternatively activated macrophages (M2) to the site of infection. Nematode infection is associated with changes in epithelial permeability and inhibition of sodium-linked glucose absorption, but the role of M2 in these effects is unknown. Clodronate-containing liposomes were administered prior to and during nematode infection to deplete macrophages and prevent the development of M2 in response to infection with Nippostrongylus brasiliensis. The inhibition of epithelial glucose absorption that is associated with nematode infection involved a macrophage-dependent reduction in SGLT1 activity, with no change in receptor expression, and a macrophage-independent down-regulation of GLUT2 expression. The reduced transport of glucose into the enterocyte is compensated partially by an up-regulation of the constitutive GLUT1 transporter consistent with stress-induced activation of HIF-1α. Thus, nematode infection results in a "lean" epithelial phenotype that features decreased SGLT1 activity, decreased expression of GLUT2 and an emergent dependence on GLUT1 for glucose uptake into the enterocyte. Macrophages do not play a role in enteric nematode infection-induced changes in epithelial barrier function. There is a greater contribution, however, of paracellular absorption of glucose to supply the energy demands of host resistance. These data provide further evidence of the ability of macrophages to alter glucose metabolism of neighboring cells.
    PLoS ONE 01/2014; 9(1):e84763. DOI:10.1371/journal.pone.0084763 · 3.23 Impact Factor
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    ABSTRACT: Liver X receptors (LXR) play an integral role in cholesterol metabolism and the inflammatory response. High-fat (HF) diets and microbial infection can antagonize the LXR pathway leading to accumulation of cholesteryl-esters (CE) and increased expression of pro-inflammatory mediators in macrophages. The probiotic bacteria Lactobacillus paracasei possesses cholesterol lowering and immune modulating properties. Therefore, the present study sought to model whether daily feeding of L. paracasei to juvenile Ossabaw pigs fed a HF diet could modulate cholesterol metabolism and the LXR/inflammatory axis in lipopolysacharide (LPS)-stimulated alveolar macrophages (AM). The results showed that AM from pigs fed a HF diet had significantly higher concentrations of CE compared to AM from pigs fed a control (C) diet, but not in pigs fed a HF diet with L. paracasei (HFPB). Ex vivo LPS stimulation of AM opposed LXR agonist-mediated transcription of cholesterol metabolism related genes: ABCA1, CH25H and PPARγ in pigs on the C diet, and LXRα, ABCA1, ABCG1, CH25H and PPARγ in pigs on the HF diet. This effect was abrogated for all these genes except LXRα in AM from pigs given L. paracasei. Protein analysis of culture supernatants revealed that AM from HFPB-fed pigs had significantly lower LPS-induced protein expression of IL-1β than AM from HF-fed pigs. Moreover, AM from pigs fed the C diet and given L. paracasei, had significantly higher mRNA levels of IL-8, and IL-6, in response to LPS. These data demonstrated a role for L. paracasei in modulating AM cholesterol metabolism and the response to LPS.
    The Journal of nutritional biochemistry 09/2013; 24(11). DOI:10.1016/j.jnutbio.2013.06.001 · 3.79 Impact Factor
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    ABSTRACT: Background/Question/Methods Most animals are concurrently infected with multiple parasites. Compelling, but limited, evidence suggests that interactions among co-infecting parasites can influence disease dynamics and host fitness. Human and laboratory animal studies provide strong evidence of resource-based and immune-based mechanisms driving interactions between pairs of parasite species. Although both mechanisms likely operate within individual hosts, most studies typically focus on each mechanism independently. Additionally, decreased condition and/or nutrition can influence an individual’s ability to mount adequate immune responses. However, it is unclear how reductions in host immunocompetence will affect both resource- and immune-mediated interactions among co-infecting parasites. To test concurrent interactions among parasites, immune function, and host nutrition, we conducted a factorial experiment using laboratory mice (Balb/c). Specifically, mice were given high or low quality diets, dosed with two species of helminths (alone and in combination), and challenged with bovine tuberculosis. Results/Conclusions We found that diet quality and co-infection status strongly influenced host immune function and condition, the proportion of supershedders, and parasite survival and reproduction. Importantly, the magnitude and direction of responses in both hosts and parasites depended on parasite species identity, diet quality, and the combination of co-infecting parasites. For example, a low-quality diet increased egg production of one helminth by 1.4-fold, but decreased egg production of the other by 2.7-fold. Also, both helminth and bovine tuberculosis co-infections increased the proportion of supershedders of one helminth, but not the other. Importantly, effects of bovine tuberculosis on helminth egg production were detectible only in mice fed the low-quality diet. Parasite reproduction influences the number of infective stages released into the environment and, consequently, transmission within host populations. Mouse weight, a correlate of condition and fecundity, increased at a lower rate during peak helminth egg production, but single infections were no more pathogenic than dual infections. However, hosts co-infected with all three parasites (two helminths + bovine tuberculosis) gained the least weight. Our findings highlight the importance of investigating parasite communities, not simply single parasites, to understand the responses of both host and parasite populations to additional pathogens and changing resource availability.
    98th ESA Annual Convention 2013; 08/2013
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    ABSTRACT: Typical clinical biomarker analyses on urine and plasma samples from human dietary interventions do not provide adequate information about diet-induced metabolic changes taking place in tissues. The aim of this study was to show how a large-scale non-targeted metabolomic approach can be used to reveal metabolite groups for generating new hypotheses of obesity-related metabolic disturbances produced in an animal model. A large spectrum of metabolites in the semi-polar region, including small water soluble molecules like betaine and dihydroxyindole, and a wide range of bile acids as well as various lipid species were detected. The high fat diet influenced metabolic homeostasis of Ossabaw pigs, especially the lipid metabolome, throughout all the analyzed sample types, including plasma, urine, bile, liver, pancreas, brain cortex, intestinal jejunum and proximal colon. However, even dramatic metabolic changes in tissues were not necessarily observed in plasma and urine. Metabolite profiling involving multiple sample types was shown to be a feasible method for the examination of a wide spectrum of metabolic species extending from small water soluble metabolites to an array of bile acids and lipids, thus pointing to the pathways of metabolism affected by the dietary treatment.
    Journal of Proteome Research 06/2013; 12(9). DOI:10.1021/pr400257d · 4.25 Impact Factor
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    ABSTRACT: Heligmosomoides bakeri is a nematode with parasitic development exclusively in the small intestine of infected mice that induces a potent STAT6-dependent Th2 immune response. We previously demonstrated that host protective expulsion of adult H. bakeri worms from a challenge infection was delayed in selenium (Se)-deficient mice. In order to explore mechanisms associated with the delayed expulsion, 3-week-old female BALB/c mice were placed on a torula yeast-based diet with or without 0.2 ppm Se, and after 5 weeks, they were inoculated with H. bakeri infective third-stage larvae (L3s). Two weeks after inoculation, the mice were treated with an anthelmintic and then rested, reinoculated with L3s, and evaluated at various times after reinoculation. Analysis of gene expression in parasite-induced cysts and surrounding tissue isolated from the intestine of infected mice showed that the local-tissue Th2 response was decreased in Se-deficient mice compared to that in Se-adequate mice. In addition, adult worms recovered from Se-deficient mice had higher ATP levels than worms from Se-adequate mice, indicating greater metabolic activity in the face of a suboptimal Se-dependent local immune response. Notably, the process of worm expulsion was restored within 2 to 4 days after feeding a Se-adequate diet to Se-deficient mice. Expulsion was associated with an increased local expression of Th2-associated genes in the small intestine, intestinal glutathione peroxidase activity, secreted Relm-β protein, anti-H. bakeri IgG1 production, and reduced worm fecundity and ATP-dependent metabolic activity.
    Infection and immunity 05/2013; 81(7). DOI:10.1128/IAI.01047-12 · 3.73 Impact Factor
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    ABSTRACT: SerpinB2, a member of the serine protease inhibitor family, is expressed by macrophages and is significantly upregulated by inflammation. Recent studies implicated a role for SerpinB2 in the control of Th1 and Th2 immune responses, but the mechanisms of these effects are unknown. In this study, we used mice deficient in SerpinB2 (SerpinB2(-/-)) to investigate its role in the host response to the enteric nematode, Heligmosomoides bakeri. Nematode infection induced a STAT6-dependent increase in intestinal SerpinB2 expression. The H. bakeri-induced upregulation of IL-4 and IL-13 expression was attenuated in SerpinB2(-/-) mice coincident with an impaired worm clearance. In addition, lack of SerpinB2 in mice resulted in a loss of the H. bakeri-induced smooth muscle hypercontractility and a significant delay in infection-induced increase in mucosal permeability. Th2 immunity is generally linked to a CCL2-mediated increase in the infiltration of macrophages that develop into the alternatively activated phenotype (M2). In H. bakeri-infected SerpinB2(-/-) mice, there was an impaired infiltration and alternative activation of macrophages accompanied by a decrease in the intestinal CCL2 expression. Studies in macrophages isolated from SerpinB2(-/-) mice showed a reduced CCL2 expression, but normal M2 development, in response to stimulation of Th2 cytokines. These data demonstrate that the immune regulation of SerpinB2 expression plays a critical role in the development of Th2-mediated protective immunity against nematode infection by a mechanism involving CCL2 production and macrophage infiltration.
    The Journal of Immunology 04/2013; 190(11). DOI:10.4049/jimmunol.1200293 · 4.92 Impact Factor

Publication Stats

11k Citations
1,648.76 Total Impact Points


  • 2003-2015
    • United States Department of Agriculture
      • Agricultural Research Service (ARS)
      Washington, Washington, D.C., United States
    • Cincinnati Children's Hospital Medical Center
      • Division of Emergency Medicine
      Cincinnati, OH, United States
  • 2014
    • Agricultural Research Service
      ERV, Texas, United States
  • 2010
    • University of Maryland, Baltimore
      • Department of Medicine
      Baltimore, Maryland, United States
    • Maryland Department Of Agriculture
      Annapolis, Maryland, United States
  • 2008-2009
    • Le Centre de Recherche en Nutrition Humaine Rhône-Alpes
      Rhône-Alpes, France
    • The Rockefeller University
      New York City, New York, United States
    • Texas College
      College Station, Texas, United States
  • 2007
    • University of Texas Medical Branch at Galveston
      Galveston, Texas, United States
  • 1991-2007
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Parasitic Diseases (LPD)
      Maryland, United States
  • 2006
    • Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland
  • 1986-2006
    • Uniformed Services University of the Health Sciences
      • • Department of Medicine
      • • Department of Pediatrics
      • • Department of Microbiology & Immunology
      • • Department of Pathology
      베서스다, Maryland, United States
  • 2005
    • University of Iowa
      • Department of Internal Medicine
      Iowa City, Iowa, United States
  • 2004
    • University of California, San Francisco
      • Department of Microbiology and Immunology
      San Francisco, California, United States
  • 1996-2001
    • University of Cincinnati
      Cincinnati, Ohio, United States
  • 1962
    • University of Massachusetts Boston
      Boston, Massachusetts, United States