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Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection

Author:
Rolig, Annah S., Carter, J. Elliot, Ottemann, Karen M.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.49 pp. 19749-19754
ISSN:
0027-8424
Subject:
CD4-positive T-lymphocytes, Citrobacter rodentium, Helicobacter pylori, apoptosis, bacterial infections, chemotaxis, fluorescent antibody technique, immune response, inflammation, messenger RNA, mutants, niches, pathogens, recruitment
Abstract:
The host inflammatory response to chronic bacterial infections often dictates the disease outcome. In the case of the gastric pathogen Helicobacter pylori, host inflammatory responses result in outcomes that range from moderate and asymptomatic to more severe with concomitant ulcer or cancers. It was found recently that H. pylori chemotaxis mutants (Che–), which lack directed motility but colonize to nearly wild-type levels, trigger less host inflammation. We used these mutants to observe host immune responses that resulted in reduced disease states. Here we report that these mutants are defective for early gastric recruitment of CD4+ T cells compared with wild-type infection. Furthermore, Che– mutant infections lack the T-helper cell, type 17 (Th17) component of the immune response, as measured by cytokine mRNA levels in gastric tissue via intracellular cytokine staining and immunofluorescence. We additionally find that a Che– mutant infection results in significantly less host cell apoptosis than does wild-type infection, in accordance with previous observations that T-helper cell, type 17 responses in Citrobacter rodentium infections are driven by concomitant bacterial and apoptotic cell signals. We propose that bacterial chemotaxis allows H. pylori to access a particular host niche that allows the bacteria to express or deliver proapoptotic host cell factors. This report indicates that chemotaxis plays a role in enhancing apoptosis, suggesting bacterial chemotaxis systems might serve as therapeutic targets for infections whose symptoms arise from host cell apoptosis and tissue damage.
Agid:
589144