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Measuring Bacterial Load and Immune Responses in Mice Infected with Listeria monocytogenes
Published on: August 9, 2011
The Second Receptor for C5a, C5aR2, Is Detrimental to Mice during Systemic Infection with Listeria monocytogenes
Stacey L Mueller-Ortiz1, Pooja Shivshankar1, Rick A Wetsel2,3
1Brown Foundation Institute of Molecular Medicine, Research Center for Immunology and Autoimmune Diseases, University of Texas Health Science Center at Houston, Houston, TX 77030; and.
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-γ in their spleens on day 1 postinfection. Purified naive splenocytes from C5aR2-/- mice produced significantly more IFN-γ and IL-12p70 during in vitro infection with L. monocytogenes compared with splenocytes from C5aR2+/+ mice in an NF-κB-dependent manner. Induction of IL-12 and IFN-γ 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-γ provided early protection to the C5aR2-/- mice.
Insights
The complement receptor C5aR2 plays a crucial role in Listeria monocytogenes infection. Deleting C5aR2 enhances host immunity, leading to reduced bacterial load and improved survival by boosting early IL-12 and IFN-γ production.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Listeria monocytogenes infection poses a significant mortality risk.
- Previous studies identified anti-inflammatory and prosurvival roles for C5aR1 and C3aR in systemic L. monocytogenes infection.
Purpose of the Study:
- To investigate the role of the anaphylatoxin receptor C5aR2 in the host immune response to systemic L. monocytogenes infection.
Main Methods:
- Comparative analysis of C5aR2 knockout (C5aR2-/-) and wild-type (C5aR2+/+) mice infected with L. monocytogenes.
- Assessment of bacterial burdens, organ damage, immune cell survival, and cytokine profiles (G-CSF, IL-6, MCP-1, IFN-γ, IL-12p70).
- In vitro infection assays with purified splenocytes to evaluate cytokine production in an NF-κB-dependent manner.
Main Results:
- C5aR2-/- mice exhibited significantly lower bacterial burdens in the spleen and liver.
- Reduced liver damage and improved CD4+ and CD8+ T cell survival were observed in C5aR2-/- mice.
- C5aR2-/- mice produced less G-CSF, IL-6, and MCP-1, but demonstrated an enhanced capacity for IL-12 and IFN-γ production in vitro, indicating a more robust early innate immune response.
Conclusions:
- C5aR2 negatively regulates the early innate immune response to systemic L. monocytogenes infection.
- The absence of C5aR2 leads to increased IL-12 and IFN-γ production, conferring protection against infection.
- Targeting C5aR2 may represent a therapeutic strategy to enhance host defense against L. monocytogenes.
