Abstract
Intra-macrophage bacterial infections cause significant morbidity and mortality in both the developed and developing world. Protective host immune responses to these infections initially requires the activation and expansion of pathogen-specific CD4 Th1 cells within lymphoid tissues and subsequent relocation of these effector cells to sites of infection. After entering infected tissues, the elicitation of Th1 bactericidal activity can be triggered by cognate or non-cognate signals that are delivered by locally infected antigen-presenting cells and innate cells. However, the contribution of non-cognate stimulation to the resolution of bacterial infection remains poorly understood, especially in the context of a Th1 response. Here, we review the current data on Th1 cell activation and expansion in mouse models of Salmonella and Chlamydia infection and discuss the potential role of non-cognate Th1 cell stimulation in these disease models. Greater understanding of this pathway of T cell activation may lead to the design of therapeutics or vaccines to combat intra-macrophage pathogens.
Highlights
The mammalian immune system contains a variety of cell types that respond in a highly coordinated fashion to eradicate microbial pathogens
The ability of these expanded effector lymphocytes to blur the lines between innate and adaptive immunity may be a critical component of protective immunity to Salmonella, Chlamydia, and other intracellular bacteria
Naïve CD4 T cells are activated by cognate signals leading to the expansion of an effector pool of pathogen-specific T cells that can migrate to infected tissues and deliver local anti-microbial effects
Summary
The mammalian immune system contains a variety of cell types that respond in a highly coordinated fashion to eradicate microbial pathogens. The contribution of CD8 T cells and B cells in resolving primary infection is thought to be limited [27, 30,31,32,33], recent data suggest a requirement for B cells in preventing bacterial dissemination to systemic tissues following Chlamydia genital challenge [28]. COGNATE SIGNALS DRIVING T CELL ACTIVATION AND REACTIVATION Naïve pathogen-specific CD4 T cells are activated in secondary lymphoid tissues by dendritic cells expressing CD80/86 and displaying microbial peptides on surface MHC class-II [40].
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