TLR2 Engagement on Dendritic Cells Promotes High Frequency Effector and Memory CD4 T Cell Responses

Abstract

Ligation of TLR by distinct pathogen components provides essential signals for T cell priming, although how individual TLR engagement affects primary and memory T cell responses is not well defined. In this study, we demonstrate distinct effects of TLR2 vs TLR4 engagement on primary and memory CD4 T cell responses due to differential effects on APC. Priming of influenza hemagglutinin (HA)-specific naive CD4 T cells with HA peptide and the TLR2 agonist Pam3CysK in vivo resulted in a high frequency of activated HA-specific CD4 T cells that predominantly produced IL-2 and IL-17, whereas priming with HA peptide and the TLR4 agonist LPS yielded a lower frequency of HA-specific CD4 T cells and predominant IFN-γ producers. TLR2 agonist priming depended on TLR2 expression by APC, as wild-type CD4 T cells did not expand in response to peptide and Pam3CysK in TLR2-deficient hosts. TLR2-mediated priming also led to an increased frequency of Ag-specific memory CD4 T cells compared with TLR4 priming and mediated enhanced secondary responses to influenza challenge. Our results show that TLR engagement on APC influences both primary and secondary CD4 T cell responses, and suggest that long-term functional capacities of T cells are set by innate signals during early phases of an infection.

Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection

“…We report that, following an initial S. aureus skin infection, clonotypic TNF/IFN-γ-producing γδ T cells expanded in skin-draining LNs and protected against a subsequent S. aureus skin challenge, which likely complements the previously characterized antibody and IL-17 responses in immunity to S. aureus skin infections (15)(16)(17)(18). This γδ T cell protective response was long lived, as it was still present at 20 weeks, similar to αβ T cell memory responses in other models (38,39). The protection was specific to γδ T cells, since transfer of γδ T cells, but not serum containing S. aureus-specific antibodies, CD4 + T cells, or primed neutrophils from previously infected IL-1β -/-mice, rescued the immune impairment of naive IL-1β -/-mice.…”

Dysregulation of Toll-Like Receptor 7 Compromises Innate and Adaptive T Cell Responses and Host Resistance to an Attenuated West Nile Virus Infection in Old Mice

“…During microbial infection, the production of type I IFNs and inflammatory cytokines induced by the recognition of PRRs via their cognate ligands is critical for control of replication, enhancement of APC functions, and influencing both primary and secondary CD4 ϩ and CD8 ϩ T cell responses (61)(62)(63)(64). They can also act directly on T cells to modulate cell proliferation, survival, and/or differentiation into effector cells both in vitro and in vivo (65)(66)(67)(68).…”

TH17-Mediated Protection against Pneumococcal Carriage by a Whole-Cell Vaccine Is Dependent on Toll-Like Receptor 2 and Surface Lipoproteins

“…The role of TLR2 in eliciting pneumococcal proteinspecific IL-17A responses was subsequently demonstrated in mice using vaccines composed of candidate pneumococcal T H 17 antigens (5). Others have more broadly demonstrated a role for TLR2 engagement during immunization to enhance the generation of antigen-specific memory CD4 ϩ T cell responses (19). We hypothesized that the immunogenicity and protective efficacy of WCV also might depend on intact host TLR2 activity.…”