Article

Parasitic Infection Improves Survival from Septic Peritonitis by Enhancing Mast Cell Responses to Bacteria in Mice

Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
PLoS ONE (Impact Factor: 3.23). 11/2011; 6(11):e27564. DOI: 10.1371/journal.pone.0027564
Source: PubMed

ABSTRACT

Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh)/Kit(W-sh) mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh)/Kit(W-sh) mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

Download full-text

Full-text

Available from: Paul J Wolters
  • Source
    • "Nevertheless , Sutherland et al. (2011) showed that co-infections with N. brasiliensis reduced bacteraemia and improved survival of septic peritonitis caused by Klebsiella pneumoniae . This protection was mediated through IL-4-condi- tioned mast cells, which led to an increased production of IL-6 and improved neutrophil recruitment after K. pneumoniae infection (Sutherland et al., 2011). Accordingly, recent studies have revealed that an E. coli challenge in chronically L. sigmodontis-infected BALB/c mice resulted in a reduced inflammation, milder hypothermia and improved bacterial clearance independent of the Mf status (F Gondorf , A Hoerauf and MP H€ ubner unpublished findings). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of autoimmune and allergic disorders has dramatically increased in developed countries, and it is believed that our ‘cleaner living’ reduces exposure to certain microorganisms and leads to deviated and/or reduced regulation of the immune system. In substantiation of this health hygiene hypothesis, multiple epidemiological studies and animal models have characterized the protective immune responses induced by helminths during auto-inflammatory disorders. The beneficial effects of such helminths, like schistosomes and filariae, are thought to lie in their immunomodulatory capacity, which can be induced by different life-cycle stages or components thereof. In addition to suppressing autoimmunity recent evidence indicates that concurrent helminth infections also counterbalance exacerbated pro-inflammatory immune responses that occur during sepsis, improving survival. As with allergy, epidemiological studies have observed a steady rise in severe sepsis cases and although this may have resulted from several factors (immunosuppressive drugs, chemotherapy, transplantation, increased awareness and increased surgical procedures), it is tempting to hypothesize that the lack of helminth infections in Western countries may have contributed to this phenomenon. This review summarizes how helminths modulate host immunity during sepsis, such as manipulating macrophage activation and provides an overview about the possible implications that may arise during overwhelming bacterial co-infections. This well written review gives a comprehensive overview on the immunopathology of sepsis and the modulation of immune responses by helminths. It provides evidence that helminths or components thereof may improve the outcome of severe infections. This will allow the development of therapeutic strategies to fight infections and sepsis.
    Full-text · Article · Aug 2013 · Pathogens and Disease
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Concern about the use of nanomaterials has increased significantly in recent years due to potentially hazardous impacts on human health. Mast cells are critical for innate and adaptive immune responses, often modulating allergic and pathogenic conditions. Mast cells are well known to act in response to danger signals through a variety of receptors and pathways including IL-33 and the IL-1-like receptor ST2. Here, the involvement of mast cells and the IL-33/ST2 axis in pulmonary and cardiovascular responses to multi-walled carbon nanotube (MWCNT) exposure are examined. Toxicological effects of MWCNTs are observed only in mice with a sufficient population of mast cells and are not observed when mast cells are absent or incapable of responding to IL-33. Our findings establish for the first time that mast cells and the IL-33/ST2 axis orchestrates adverse pulmonary and cardiovascular responses to an engineered nanomaterial, giving insight into a previously unknown mechanism of toxicity. This novel mechanism of toxicity could be used for assessing the safety of engineered nanomaterials and provides a realistic therapeutic target for potential nanoparticle induced toxicities.
    Full-text · Article · Sep 2012 · Small
  • Source
    S Li · W Li · Z Yang · S Song · J Yang · P Gong · W Zhang · K Liu · J Li · G Zhang · X Zhang
    [Show abstract] [Hide abstract]
    ABSTRACT: Mast cells might play an important role as the major effector cells in the immune response against Cryptosporidium parvum. C. parvum is a protozoan parasite that causes cryptosporidiosis in animals and humans worldwide. To investigate the interaction between C. parvum and mast cells during infection, nine 3-day-old male calves were orally challenged with 10(6) oocysts of C. parvum per calf. The distribution of mast cells in the mucosa of the small intestine was analyzed by toluidine blue staining. The concentrations of histamine and the cytokines interferon-γ, interleukin-4, interleukin-2, and interleukin-12 were measured in the serum, and the histamine levels were also determined from the intestinal contents. The following clinical signs were monitored: nausea, watery diarrhea, dehydration, and weight loss. Oocysts were shed in the feces during the infection period. C. parvum infection induced an increase in mast cell numbers in the mucosa of the small intestine in distinct temporal and spatial patterns. Infection with C. parvum can induce mastocytosis in the entire small intestinal mucosa in immune-competent calves, and the presence of the parasites influences the distribution profile of the mast cells.
    Preview · Article · Jan 2013 · Veterinary Pathology
Show more