CD4+ T Cells Are as Protective as CD8+ T Cells against Rickettsia typhi Infection by Activating Macrophage
Kristin Moderzynski1, Stefanie Papp1, Jessica Rauch1
1Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Abstract:
Rickettsia typhi is an intracellular bacterium that causes endemic typhus, a febrile disease that can be fatal due to complications including pneumonia, hepatitis and meningoencephalitis, the latter being a regular outcome in T and B cell-deficient C57BL/6 RAG1-/- mice upon Rickettsia typhi infection. Here, we show that CD4+ TH1 cells that are generated in C57BL/6 mice upon R. typhi infection are as protective as cytotoxic CD8+ T cells. CD4+- as well as CD8+-deficient C57BL/6 survived the infection without showing symptoms of disease at any point in time. Moreover, adoptively transferred CD8+ and CD4+ immune T cells entered the CNS of C57BL/6 RAG1-/- mice with advanced infection and both eradicated the bacteria. However, immune CD4+ T cells protected only approximately 60% of the animals from death. They induced the expression of iNOS in infiltrating macrophages as well as in resident microglia in the CNS which can contribute to bacterial killing but also accelerate pathology. In vitro immune CD4+ T cells inhibited bacterial growth in infected macrophages which was in part mediated by the release of IFNγ. Collectively, our data demonstrate that CD4+ T cells are as protective as CD8+ T cells against R. typhi, provided that CD4+ TH1 effector cells are present in time to support bactericidal activity of phagocytes via the release of IFNγ and other factors. With regard to vaccination against TG Rickettsiae, our findings suggest that the induction of CD4+ TH1 effector cells is sufficient for protection.
Insights
CD4+ TH1 cells are as protective as CD8+ T cells against Rickettsia typhi infection. These immune cells help control bacteria by activating phagocytes, suggesting CD4+ TH1 induction is sufficient for protection.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Rickettsia typhi causes endemic typhus, a potentially fatal febrile illness.
- Complications include pneumonia, hepatitis, and meningoencephalitis, particularly in immunodeficient mice.
- T and B cell deficiency in C57BL/6 RAG1-/- mice leads to severe outcomes upon R. typhi infection.
Purpose of the Study:
- To investigate the protective roles of CD4+ and CD8+ T cells against Rickettsia typhi.
- To determine if CD4+ TH1 cells offer protection comparable to CD8+ T cells.
- To explore the mechanisms by which CD4+ T cells mediate protection and influence pathology.
Main Methods:
- Infection of C57BL/6 mice with Rickettsia typhi.
- Analysis of CD4+ and CD8+ T cell responses.
- Adoptive transfer of immune T cells into RAG1-/- mice.
- Assessment of bacterial eradication and survival rates.
- In vitro studies on T cell-mediated inhibition of bacterial growth in macrophages.
Main Results:
- CD4+ TH1 cells provided protection comparable to CD8+ T cells against R. typhi infection.
- Adoptively transferred CD4+ and CD8+ T cells eradicated bacteria in the CNS of infected RAG1-/- mice.
- CD4+ T cells induced iNOS in CNS macrophages and microglia, contributing to bacterial killing but also pathology.
- In vitro, CD4+ T cells inhibited R. typhi growth in macrophages, partly via IFNγ release.
- CD4+- and CD8+-deficient mice survived R. typhi infection without symptoms.
Conclusions:
- CD4+ T cells are as protective as CD8+ T cells against R. typhi when TH1 effector cells are timely induced.
- CD4+ TH1 cells support phagocyte bactericidal activity through IFNγ and other factors.
- Induction of CD4+ TH1 effector cells appears sufficient for protection against Rickettsia typhi.
- These findings have implications for vaccination strategies against typhus group Rickettsiae.
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