RESUMO
CD4+ T lymphocytes are crucial for controlling a range of innate and adaptive immune effectors. For CD8+ cytotoxic T lymphocyte (CTL) responses, CD4+ T cells can function as helpers (TH) to amplify magnitude and functionality or as regulatory cells (Treg) capable of profound inhibition. It is unclear what determines differentiation to these phenotypes and whether pathogens provoke alternate programs. We find that, depending on the size of initial dose, Listeria infection drives CD4+ T cells to act as TH or induces rapid polyclonal conversion to immunosuppressive Treg. Conversion to Treg depends on the TLR9 and IL-12 pathways elicited by CD8α+ dendritic cell (DC) sensing of danger-associated neutrophil self-DNA. These findings resolve long-standing questions regarding the conditional requirement for TH amongst pathogens and reveal a remarkable degree of plasticity in the function of CD4+ T cells, which can be quickly converted to Tregin vivo by infection-mediated immune modulation.
Assuntos
Linfócitos T CD4-Positivos/imunologia , DNA/imunologia , Listeriose/imunologia , Linfócitos T Reguladores/imunologia , Receptor Toll-Like 9/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , DNA/genética , Células Dendríticas/imunologia , Feminino , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/genética , Imunidade Celular/imunologia , Interleucina-12/biossíntese , Interleucina-12/genética , Interleucina-12/imunologia , Listeria monocytogenes/imunologia , Listeriose/genética , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Receptor Toll-Like 9/genéticaRESUMO
Plants have evolved a variety of mechanisms to respond and adapt to abiotic stress. High temperature stress induces the heat shock response. During the heat shock response a large number of genes are up-regulated, many of which code for chaperone proteins that prevent irreversible protein aggregation and cell death. However, it is clear that heat shock is not the only mechanism involved in the plant heat stress response. Alternative splicing (AS) is also important during heat stress since this post-transcriptional regulatory mechanism can produce significant transcriptome and proteome variation. In this study, we examine AS during heat stress in the model species Arabidopsis thaliana and in the highly thermotolerant native California mustard Boechera depauperata. Analyses of AS during heat stress revealed that while a significant number of genes undergo AS and are differentially expressed (DE) during heat stress, some undergo both AS and DE. Analysis of the functional categories of genes undergoing AS indicated that enrichment patterns are different in the two species. Categories enriched in B. depauperata included light response genes and numerous abiotic stress response genes. Categories enriched in A. thaliana, but not in B. depauperata, included RNA processing and nucleotide binding. We conclude that AS and DE are largely independent responses to heat stress. Furthermore, this study reveals significant differences in the AS response to heat stress in the two related mustard species. This indicates AS responses to heat stress are species-specific. Future studies will explore the role of AS of specific genes in organismal thermotolerance.
