Javier Rangel-Moreno

University of Rochester | UR · School of Medicine and Dentistry

Translating genome-wide association study (GWAS) loci into causal variants and genes requires accurate cell-type-specific enhancer-gene maps from disease-relevant tissues. Building enhancer-gene maps is essential but challenging with current experimental methods in primary human tissues. Here we developed a nonparametric statistical method, SCENT (...

Tuberculosis (TB) caused by Mycobacterium tuberculosis ( Mtb ) infects up to a quarter of the world’s population. Although immune responses can control Mtb infection, 5%–10% of infected individuals can progress to active TB disease (progressors). A myriad of host factors regulate disease progression in TB and a better understanding of immune correl...

Influenza is a highly contagious, acute respiratory disease that causes significant public health and economic threats. Influenza infection induces various inflammatory mediators, IFNs, and recruitment of inflammatory cells in the host. This inflammatory “cytokine storm” is thought to play a role in influenza-induced lung pathogenesis. Empagliflozi...

The human leukocyte antigen (HLA) locus plays a critical role in complex traits spanning autoimmune and infectious diseases, transplantation and cancer. While coding variation in HLA genes has been extensively documented, regulatory genetic variation modulating HLA expression levels has not been comprehensively investigated. Here we mapped expressi...

Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction ¹ . There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity 1,2 . Here, to deconstruct the cell states and pathways that characterize this path...

Introduction Defective lymphatic drainage and translocation of B-cells in inflamed (Bin) joint-draining lymph node sinuses are pathogenic phenomena in patients with severe rheumatoid arthritis (RA). However, the molecular mechanisms underlying this lymphatic dysfunction remain poorly understood. Herein, we utilized multi-omic spatial and single-cel...

The ADP ribosyl transferases (PARPs 1-17) regulate diverse cellular processes, including DNA damage repair. PARPs are classified based on their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). While PARP9 mRNA expression is significantly increased in progressive human tuberculosis (TB), its participation...

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause of death. Granuloma-associated lymphoid tissue (GrALT) correlates with protection during TB, but the mechanisms of protection are not understood. During TB, the transcription factor IRF4 in T cells but not B cells is required for the generation of the TH1 and TH17 subs...

While recent studies showed that macrophages are critical for bone fracture healing, and lack of M2 macrophages have been implicated in models of delayed union, functional roles for specific M2 receptors have yet to be defined. Moreover, the M2 scavenger receptor CD163 has been identified as a target to inhibit sepsis following implant associated o...

Objective Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is essential for the formation of fully functional multinucleated osteoclasts. DC-STAMP deficient mice, under physiological conditions, exhibit osteopetrosis and develop systemic autoimmunity with age. However, the function of DC-STAMP in inflammation is currently unknown. We examin...

Defective lymphatic drainage and B-cell translocation into joint-draining lymph node sinuses are pathogenic phenomena in patients with severe rheumatoid arthritis (RA). However, the molecular mechanisms underlying this lymphatic dysfunction remain poorly understood. Here, by utilizing spatial and single-cell transcriptomics in tumor necrosis factor...

Tuberculosis (TB) caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb) is one of the most lethal infectious diseases in the world. Presently, Bacillus Calmette-Guerin, the vaccine approved for use against TB, does not offer complete protection against the disease, which necessitates the development of new therapeutics to treat this i...

Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial, and its role in patients with S. aureus osteomyelitis is unknown. To address this knowledge gap, we completed a clinical study and observed elevated serum IL-27 levels (20-fold higher, P < 0.05) in patients compared with healthy controls. Rema...

Ectopic lymphoid structures (ELS) can develop in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and selection are not well understood. Here, we identify a synovial B cell population characterized by co-expression of a family of orphan nuclear receptors (NR4A1-3), which is highly enriched in RA synovial tiss...

Development of an effective HIV vaccine is dependent on the quantity and quality of HIV Envelope specific antibody at the mucosal sites. Priming of the oral mucosa is a promising approach to generate mucosal antibody at HIV entry sites. Our recent work in mice has demonstrated the ability of IL-9 and IL-33, known regulators of mucosal immunity, to...

Objective: To investigate the hypothesis that selective inhibitors of nuclear export (SINE), recently approved for the treatment of refractory plasma cell (PC) malignancy, may have potential in the treatment of lupus. Methods: NZB/NZW female mice were treated with SINE or vehicle control. Tissue was harvested and analyzed by flow cytometry using...

Rheumatoid arthritis (RA) is a prototypical autoimmune disease that causes destructive tissue inflammation in joints and elsewhere. Clinical challenges in RA include the empirical selection of drugs to treat patients, inadequate responders with incomplete disease remission, and lack of a cure. We profiled the full spectrum of cells in inflamed syno...

Despite the eradication of variola virus (VARV), the causative agent of smallpox, poxviruses still represent an important threat to human health due to their possible use as bioterrorism agents and the emergence of zoonotic poxvirus diseases. Recombinant vaccinia viruses (rVV) expressing easily traceable fluorescent or luciferase reporter genes hav...

Induction of broadly neutralizing antibodies (bNAbs) is a major goal for HIV vaccine development. HIV envelope glycoprotein (Env)-specific bNAbs isolated from HIV-infected individuals exhibit substantial somatic hypermutation and correlate with T follicular helper (Tfh) responses. Using the VC10014 DNA-protein co-immunization vaccine platform consi...

Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell-and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocy...

Tissue-resident memory (TRM) cells are thought to play a role in lung mucosal immunity to pathogens, but strategies to elicit TRM by mucosal vaccines have not yet been fully realized. Here, we formulated a vaccine composed of outer membrane protein (Omp) X from Klebsiella pneumoniae and LTA1 adjuvant that was administered by the intrapulmonary rout...

Host immunity to Mycobacterium leprae encompasses a spectrum of mechanisms that range from cellular immunity-driven protection to damage associated with humoral immunity as in type-2 leprosy reactions. Although type I interferons (IFNs) participate in eliminating intracellular pathogens, their contribution to the production of antibodies and CD3+ F...

Recombinant viruses expressing reporter genes allow visualization and quantification of viral infections and can be used as valid surrogates to identify the presence of the virus in infected cells and animal models. However, one of the limitations of recombinant viruses expressing reporter genes is the use of either fluorescent or luciferase protei...

Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (Mtb) infection is urgently needed. Early and superior Mtb control can be induced in M. bovis Bacillus Calmette-Guérin (BCG)-vaccinated hosts when the inn...

Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis ( Mtb ) infection is urgently needed. Early and superior Mtb control can be induced in M. bovis Bacillus Calmette–Guérin (BCG) vaccinated hosts when the i...

Ectopic lymphoid structures (ELS) can develop in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and selection are not well understood. Here, we identified a unique B cell population in the synovium characterized by co-expression of a family of orphan nuclear receptors, NR4A1 (also known as NUR77), NR4A2 (NU...

With mortality rates ranging from 30% to 70%, carbapenem-resistant Klebsiella pneumoniae (Kp) is a significant public health threat. With growing incidence of drug resistance, it is imperative to develop alternative strategies to combat these severe infections. One novel immunotherapy is adoptive T cell transfer therapy using T cells genetically mo...

Staphylococcus aureus is the predominant pathogen causing osteomyelitis. Unfortunately, no immunotherapy exists to treat these very challenging and costly infections despite decades of research, and numerous vaccine failures in clinical trials. This lack of success can partially be attributed to an overreliance on murine models where the immune cor...

Ectopic lymphoid structures (ELS) can develop in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and selection are not well understood. Here, we identify a synovial B cell population characterized by co-expression of a family of orphan nuclear receptors (NR4A1-3), which is highly enriched in RA synovial tiss...

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) latently infects approximately one-fourth of the world’s population. The immune mechanisms that govern progression from latent (LTBI) to active pulmonary TB (PTB) remain poorly defined. Experimentally Mtb-infected non-human primates (NHP) mirror the disease observed in humans and recapit...

Background In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis–driven renal scarring r...

Inducible Bronchus Associated Lymphoid Tissue (iBALT) is an ectopic lymphoid tissue associated with severe forms of chronic lung diseases, including chronic obstructive pulmonary disease, rheumatoid lung disease, hypersensitivity pneumonitis and asthma, suggesting that iBALT may exacerbate these clinical conditions. However, despite the link betwee...

Cryptococcus neoformans is a fungal pathogen that kills almost 200,000 people each year and is distinguished by abundant and unique surface glycan structures that are rich in xylose. A mutant strain of C. neoformans that cannot transport xylose precursors into the secretory compartment is severely attenuated in virulence in mice, yet surprisingly i...

Mycobacterium tuberculosis (Mtb) is the causative agent of the infectious disease tuberculosis (TB), which is a leading cause of death worldwide. Approximately one fourth of the world's population is infected with Mtb. A major unresolved question is delineating the inducers of protective long-lasting immune response without inducing overt, lung inf...

The aerosol infection of mice with lab-adapted Mycobacterium tuberculosis (Mtb) strains in not an ideal model to study the immune parameters crucial for structural organization of protective human tuberculosis (TB) granulomas. Since experimentation in larger animals that mimic human lung granulomatous responses is expensive, a cost-effective animal...

Mycobacterium tuberculosis (Mtb) is the leading cause of death by infectious agent in the world today, infecting roughly ¼ of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized. Lung resident Alveolar Macrophages (AMs) are the first host contact with Mt...

Systemic lupus erythematous (SLE) is a complex autoimmune disease affecting multiple organs. Anti-nuclear antibody (Ab) producing plasma cells (PCs) play a critical role in the disease pathogenesis and are an important target for developing therapies against SLE. Karyopharm Therapeutics (KPTI) is an oncology-focused pharmaceutical company dedicated...

Objective Mucosal immunization with a Klebsiella pneumoniae (Kp) vaccine elicits noble CXCR6+CD4+ T cells that mediate serotype independent immunity, but the stability of this response is unclear. Thus we conducted experiments to determine if these cells circulate and whether they could be depleted by a depleting anti-GK1.5 mAb. Methods Mice were...

Neutrophil accumulation is associated with lung pathology during active tuberculosis (ATB). However, the molecular mechanism(s) by which neutrophils accumulate in the lung and contribute to TB immunopathology is not fully delineated. Using the well-established mouse model of TB, our new data provides evidence that the alarmin S100A8/A9 mediates neu...

Background SLE is an autoimmune disease characterized by activation of the innate and adaptive arms of the immune system. Recently the nuclear export protein exportin-1 (XPO1) has surfaced as an attractive target for the treatment of SLE. Verdinexor is a potent, orally available and well-tolerated XPO1 inhibitor. Verdinexor inhibits the nuclear exp...

Chronic inflammation promotes progression of many cancers, with circulating myeloid-derived suppressor cell (MDSC) levels correlating with poor prognosis. Here we examine effects of MDSCs on lymphangioleiomyomatosis (LAM), a rare disease occurring almost exclusively in women whereby estrogen-sensitive metastatic TSC2-null tumors grow throughout the...

One quarter of the world’s population is infected with Mycobacterium tuberculosis ( Mtb ), the causative agent of tuberculosis (TB). Although most infected individuals successfully control or clear the infection, some individuals will progress to TB disease. Immune correlates identified using animal models are not always effectively translated to h...

Specific spatial organization of granulomas within the lungs is crucial for protective anti-tuberculosis (TB) immune responses. However, only large animal models such as macaques are thought to reproduce the morphological hallmarks of human TB granulomas. In this study, we show that infection of mice with clinical "hypervirulent" Mycobacterium tube...

Cryptococcus neoformans is a fungal pathogen that kills almost 200,000 people each year and is distinguished by abundant and unique surface glycan structures that are rich in xylose. A mutant strain of C. neoformans that cannot transport xylose precursors into the secretory compartment is severely attenuated in virulence in mice, yet surprisingly i...

Influenza A viruses (IAVs) cause human respiratory disease that is associated with significant health and economic consequences. As with other viruses, studying IAV requires the use of laborious secondary approaches to detect the presence of the virus in infected cells and/or in animal models of infection. This limitation has been recently circumve...

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an i...

Tuberculosis is the leading cause of death by an infectious disease worldwide¹. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and restored...

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by simultaneous activation of the innate and adaptive arms of the immune system. Recently the nuclear export protein exportin-1 (XPO1) has surfaced as an attractive target for the treatment of SLE and other autoimmune disorders. Selective Inhibitor of Nuclea...

Susceptibility to chronic beryllium (Be) disease is linked to HLA-DP molecules possessing a glutamic acid at the 69th position of the β-chain (βGlu69), with the most prevalent βGlu69-containing molecule being HLA-DP2. We have previously shown that HLA-DP2 transgenic (Tg) mice exposed to Be oxide (BeO) develop mononuclear infiltrates in a peribronch...

Influenza A virus (IAV) causes a human respiratory disease that is associated with significant health and economic consequences. In recent years, the use of replication-competent IAV expressing an easily traceable fluorescent or luciferase reporter protein has significantly contributed to progress in influenza research. However, researchers have be...

Susceptibility to chronic beryllium disease (CBD)is linked to HLA-DP molecules possessing a glutamic acid at the 69thposition of the β-chain (βGlu69), with the most prevalent βGlu69-containing molecule being HLA-DP2. We have previously shown that exposure of HLA-DP2 transgenic mice to beryllium oxide (BeO) results in the development of mononuclear...

Objective Multidrug-resistant of Klebsiella pneumoniae (K. pneumoniae) has emerged as a global threat. Vaccination for at high-risk populations could be a promising strategy to prevent and control the disease. Methods Mice were vaccinated via intranasal with a monovalent vaccine encoding Kp serotype 2 OMPx or a quadrivalent vaccine encoding OmpC,...

Objective We demonstrated the serotype independent immunity of Klebsiella pneumoniae (K. pneumoniae) vaccine. We would like to declare next if the noble effect is dependent on the antibody specific manner. Methods Mice were vaccinated via intranasal with Kp serotype 2 OMPx adjuvanted with heat-labile enterotoxin A1 domain (LTA1) and boosted at 3 w...

Lymphangioleiomyomatosis (LAM) is a rare disease occurring almost exclusively in women whereby metastatic smooth-muscle cell-like adenomas grow within the lungs, resulting in loss of pulmonary function. LAM cells contain mutations in tuberous sclerosis 1 or 2 genes (TSC1 or TSC2), which leads to heightened mammalian target of rapamycin complex1 (mT...

Objective To examine and quantify the sexual dimorphism in musculoskeletal and cardiopulmonary pathologies in the TNF‐Tg (Tg3647) mouse model of inflammatory‐erosive arthritis. Methods Kaplan‐Meier estimates of male and female Tg3647 and WT littermates were determined. Longitudinal and cross‐sectional outcomes of musculoskeletal and cardiopulmonar...

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by simultaneous activation of the innate and adaptive arms of the immune system. Recently, the nuclear export protein exportin-1 (XPO1) has surfaced as an attractive target for the treatment of SLE. Selective Inhibitor of Nuclear Export (SINE) compounds such...

Granulocytic myeloid infiltration and resultant enhanced neutrophil elastase (NE) activity is associated with poor outcomes in numerous malignancies. We recently showed that NE expression and activity from infiltrating myeloid cells was high in human prostate cancer xenografts and mouse Pten-null prostate tumors. We further demonstrated that NE dir...

The function of B cells in osteoblast (OB) dysfunction in rheumatoid arthritis (RA) has not been well-studied. Here we show that B cells are enriched in the subchondral and endosteal bone marrow (BM) areas adjacent to osteocalcin⁺ OBs in two murine RA models: collagen-induced arthritis and the TNF-transgenic mice. Subchondral BM B cells in RA mice...

In the version of this Letter originally published, in Fig. 2d, in the third graph, the label for the y axis was incorrect as ‘TNF-α (pg ml–1)’; it should have read ‘IL-1β (pg ml–1)’. This has now been corrected.

Tuberculosis is a significant global health threat, with one-third of the world's population infected with its causative agent Mycobacterium tuberculosis (Mtb). The emergence of multidrug-resistant (MDR) Mtb that is resistant to the frontline anti-tubercular drugs rifampicin and isoniazid forces treatment with toxic second-line drugs. Currently, ~4...

Influenza is a common respiratory virus that infects between 5 and 20% of the US population and results in 30,000 deaths annually. A primary cause of influenza-associated death is secondary bacterial pneumonia. We have previously shown that influenza induces type I interferon (IFN)-mediated inhibition of Type 17 immune responses, resulting in exace...

Stat2−/− mice have deficient type I IFN responses with preserved type II IFN responses. (A) WT and Stat2−/− male 6–8 weeks mice were infected with 100 PFU of influenza A/PR/8/H1N1 by oropharyngeal aspiration for 6 days then challenged with 5 × 107 cfu of MRSA by oropharyngeal aspiration for one additional day. Overall gene expression was measured i...

No differences in Th17 response between WT and Stat2−/− mice following MRSA, and influenza-MRSA super-infection. WT or Stat2−/− mice were infected with 100 PFU of influenza A/PR/8/H1N1 or PBS by oropharyngeal aspiration for 6 days then challenged with 5 × 107 cfu of MRSA or PBS by oropharyngeal aspiration for one additional day. Frequency of (A) IL...

M1 and M2 macrophages are altered in Stat2−/− mice in response to Arg1 and IFNγ neutralization during influenza-MRSA super-infection. WT or Stat2−/− mice were infected with 100 PFU of influenza for 6 days then challenged with 5 × 107 cfu of MRSA for one additional day. Mice were treated with 300 μg of anti-IFNγ antibodies or 300 μg of rat IgG isoty...

Increased influenza burden in cells from non-hematopoietic compartments of Stat2−/− mice. WT BMC (Thy1.1 host, Thy 1.2 BM or Thy 1.2 host, Thy 1.1 BM), Stat2−/− BMC (Stat2−/− host, Stat2−/− BM), Hematopoietic Stat2−/− BMC mice (Thy 1.1 or Thy 1.2 host, Stat2−/− BM), non-hematopoietic Stat2−/− BMC (Stat2−/− host, Thy 1.1 or Thy 1.2 BM) were generate...

Stat2−/− mice have altered other STAT1 and STA6 signaling pathways during influenza-bacterial super-infection. WT or Stat2−/− mice were infected with either 100 PFU of influenza A PR/8/H1N1 or influenza for 6 days and then challenged with 5 × 107 cfu of MRSA by oropharyngeal aspiration for one additional day, (A) Stat1, (B) Stat6, (C) Pparg gene ex...

C-C motif chemokine receptor 2 (CCR2) is a major chemokine axis that recruits myeloid cells including monocytes and macrophages. Thus far, CCR2-/- mice have not been found to be susceptible to infection with Mycobacterium tuberculosis (Mtb). Here, using a prototype W-Beijing family lineage 2 Mtb strain, HN878, we show that CCR2-/- mice exhibit incr...

C-C motif chemokine receptor 2 (CCR2) axis is a major chemokine axis that recruits myeloid cells including monocytes and macrophages. Thus far, CCR2−/− mice have not been found to be more susceptible to infection with Euro-American lineage 4 strains of Mycobacterium tuberculosis (Mtb). Here, using a prototype W-Beijing family lineage 2 clinical Mtb...

Histone deacetylase 2 (HDAC2), a critical determinant of chromatin remodeling, is reduced as a consequence of oxidative stress-mediated DNA damage and impaired repair. Cigarette smoke (CS) exposure causes DNA damage and cellular senescence. However, no information is available on the role of HDAC2 in CS-induced DNA damage, stress-induced premature...

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and p...

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) is contracted via aerosol infection, typically affecting the lungs. Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only licensed vaccine and has variable efficacy in protecting against pulmonary TB. Additionally, chemotherapy is associated with low compliance contributing to d...

Loss of IL-22 increases IL17+ lymphocytes during acute and chronic stages of Mtb HN878 infection Il22-/- and B6 mice were aerosol infected with ∼500 CFU of Mtb HN878 and lungs harvested at day 30 and 100 p.i. The total number of (a) CD3+CD4+CD44hiIFNγ+, (b) CD3+CD8+CD44hiIFNγ+ (c) CD3+CD4+CD44hIL17+, (d) CD3+CD8+CD44hiIL17+. n=5. *P ≤ 0.05, **P ≤ 0...

Multiple cell types contribute to IL-22 production during HN878 infection in vitro B6 lung cells (1×106 cells) were infected with Mtb HN878 at a MOI of 0.1 and analysed for (a,b) IL-22+ lymphocytes cells at day 3 and 6 p.i.. n=3-4 for each time point. All comparisons are to base line uninfected samples. *P ≤ 0.05, **P ≤ 0.01, Student's t test.

Loss of IL-22 during chronic infection leads to decreases in alveolar and recruited macrophage populations Il22-/- and B6 mice were aerosol infected with ∼100 CFU of Mtb HN878 and lungs harvested at day 30 and 100 p.i.. The total number of (a) alveolar macrophages (AMs), myeloid dendritic cells (MDCs) (b) monocytes (Mn), (c) recruited macrophages (...

Neutrophils are well characterized as mediators of peripheral tissue damage in lupus, but it remains unclear whether they influence loss of self-tolerance in the adaptive immune compartment. Lupus neutrophils produce elevated levels of factors known to fuel autoantibody production, including IL-6 and B cell survival factors, but also reactive oxyge...

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by simultaneous activation of the innate and adaptive arms of the immune system. The progression of the disease is unpredictable, making its treatment a challenge. Recently the nuclear export protein Exportin 1 (XPO1, also known as CRM1) has surfaced as an a...

Objective Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and fu...

Labeling of proliferating immune cells by antibodies specific for Ki-67 and proliferating cell nuclear antigen (PCNA). Consecutive serial sections of the same tonsil were stained with antibodies against (A) PCNA, CD8, and CD20 or (B) Ki-67, CD8, and CD20. Representative 200× pictures of triple immunofluorescent stain for Ki-67, PCNA, and CD20 are s...

Measurement of areas covered by cells expressing prostate stem cell antigen (PSCA) (A) and CXCL10 (B) in prostatectomies. To calculate the areas covered by PSCA+ and CXCL10+ cells in panoramic tumor areas, 3 × 3 mosaic pictures were taken with the Zeiss Axioplan microscope (1.043 mm2). Areas covered by PSCA and CXCL10 in JPGE panoramic pictures wer...

Tissue infiltration and elevated peripheral circulation of granulocytic myeloid-derived cells is associated with poor outcomes in prostate cancer and other malignancies. Although myeloid-derived cells have the ability to suppress T-cell function, little is known about the direct impact of these innate cells on prostate tumor growth. Here, it is rep...

Influenza is a common contagious respiratory illness that affects people worldwide. Secondary bacterial infection is a major complication during influenza infection that causes significant morbidity and mortality. We have previously shown that influenza induces type I interferon (IFN)-mediated inhibition of Type17 immune responses, resulting in exa...

Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a leading cause of global morbidity and mortality. The only licensed TB vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), has variable efficacy in protecting against pulmonary TB. Thus, the development of more effective TB vaccines is critical to control the TB epi...

Approximately 2 billion people are infected with Mycobacterium tuberculosis (Mtb), resulting in 1.4 million deaths every year. Among Mtb-infected individuals, clinical isolates belonging to the W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is e...

Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid structure composed of highly organized T cell and B cell zones that forms in the lung in response to infectious or inflammatory stimuli. Here, we develop a model for fungal-mediated iBALT formation, using infection with Pneumocystis that induces development of pulmonary ly...

Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping...

The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen presentation and activation of vaccine-induced CD4+ T-cel...

Supplementary Figures and Supplementary Tables