The Second Receptor for C5a, C5aR2, Is Detrimental to Mice during Systemic Infection with Listeria monocytogenes.

ABSTRACT: Infection with Listeria monocytogenes is acquired through ingestion of contaminated foods and may lead to systemic infection and possible death, with an overall 20% mortality rate. Our previous work using C5aR1-/- mice and C3aR-/- mice demonstrated that C5aR1 and C3aR both play powerful anti-inflammatory and prosurvival roles during systemic infection with L. monocytogenes In our current study, we have examined the role of the third anaphylatoxin receptor, C5aR2, in the host immune response to systemic L. monocytogenes infection. C5aR2-/- mice had significantly lower bacterial burdens in the spleens and livers on both day 1 and 3 postinfection compared with C5aR2+/+ mice. The decreased bacterial burdens in the C5aR2-/- mice correlated with less liver damage and with improved survival of CD4+ and CD8+ T cells in the spleen on day 3 postinfection compared with C5aR2+/+ mice. C5aR2-/- mice also produced significantly less G-CSF, IL-6, and MCP-1 in the serum, spleen, and liver on day 1 postinfection compared with C5aR2+/+ mice. C5aR2-/- and C5aR2+/+ mice produced similar amounts of IFN-? in their spleens on day 1 postinfection. Purified naive splenocytes from C5aR2-/- mice produced significantly more IFN-? and IL-12p70 during in vitro infection with L. monocytogenes compared with splenocytes from C5aR2+/+ mice in an NF-?B-dependent manner. Induction of IL-12 and IFN-? early during infection with L. monocytogenes is protective to the host, and we believe this innate increased ability to produce more IL-12 and IFN-? provided early protection to the C5aR2-/- mice.

SUBMITTER: Mueller-Ortiz SL 

PROVIDER: S-EPMC6861014 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature