Cellular requirements for systemic control of Salmonella enterica serovar Typhimurium infections in mice

Kupz, Andreas, Bedoui, Sammy, and Strugnell, Richard A. (2014) Cellular requirements for systemic control of Salmonella enterica serovar Typhimurium infections in mice. Infection and Immunity, 82 (12). pp. 4997-5004.

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Abstract

The rational design of vaccines requires an understanding of the contributions of individual immune cell subsets to immunity. With this understanding, targeted vaccine delivery approaches and adjuvants can be developed to maximize vaccine efficiency and to minimize side effects (S. H. E. Kaufmann et al., Immunity 33:555-577, 2010; T. Ben-Yedidia and R. Arnon, Hum. Vaccines 1:95-101, 2005). We have addressed the contributions of different immune cell subsets and their ability to contribute to the control and clearance of the facultative intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) in a murine model. Using a systematic and reproducible model of experimental attenuated S. Typhimurium infection, we show that distinct lymphocyte deficiencies lead to one of four different infection outcomes: clearance, chronic infection, early death, or late death. Our study demonstrates a high level of functional redundancy in the ability of different lymphocyte subsets to provide interferon gamma (IFN-γ), a critical cytokine in Salmonella immunity. Whereas early control of the infection was entirely dependent on IFN-γ but not on any particular lymphocyte subset, clearance of the infection critically required CD4(+) T cells but appeared to be independent of IFN-γ. These data reinforce the idea of a bimodal immune response against Salmonella: an early T cell-independent but IFN-γ-dependent phase and a late T cell-dependent phase that may be IFN-γ independent.

Item ID: 36623
Item Type: Article (Research - C1)
ISSN: 1098-5522
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC program grant: Fighting Infection, Exploiting Host-Pathogen Interactions APP606788
Date Deposited: 10 Dec 2014 03:12
FoR Codes: 06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 40%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060503 Microbial Genetics @ 20%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 45%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 35%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 20%
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