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


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.

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    • "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). "
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