RESUMO
Naive CD4+ T cells in specific pathogen-free (SPF) mice are characterized by transcriptional heterogeneity and subpopulations distinguished by the expression of quiescence, the extracellular matrix (ECM) and cytoskeleton, type I interferon (IFN-I) response, memory-like, and T cell receptor (TCR) activation genes. We demonstrate that this constitutive heterogeneity, including the presence of the IFN-I response cluster, is commensal independent insofar as being identical in germ-free and SPF mice. By contrast, Nippostrongylus brasiliensis infection altered this constitutive heterogeneity. Naive T cell-intrinsic transcriptional changes acquired during helminth infection correlated with and accounted for decreased immunization response to an unrelated antigen. These compositional and functional changes were dependent variables of helminth infection, as they disappeared at the established time point of its clearance in mice. Collectively, our results indicate that the naive T cell pool is subject to dynamic transcriptional changes in response to certain environmental cues, which in turn permutes the magnitude of the immune response.
Assuntos
Linfócitos T CD4-Positivos , Nippostrongylus , Animais , Camundongos , Linfócitos T CD4-Positivos/imunologia , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia , Organismos Livres de Patógenos Específicos , Transcrição Gênica , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Helmintíase/imunologia , Interferon Tipo I/metabolismo , Interferon Tipo I/imunologia , Camundongos Endogâmicos C57BL , Ativação Linfocitária/imunologiaAssuntos
Interleucina-33 , Tirosina Quinase da Agamaglobulinemia , Humanos , Inflamação , MacrófagosRESUMO
Type 2 immunity encompasses the mechanisms through which the immune system responds to helminths and an array of environmental substances such as allergens. In the developing world, billions of individuals are chronically infected with endemic parasitic helminths. In comparison, in the industrialized world, millions of individuals suffer from dysregulated type 2 immunity, referred to clinically as atopic diseases including asthma, allergic rhinitis, and atopic dermatitis. Thus, type 2 immunity must be carefully regulated to mount protective host responses yet avoid inappropriate activation and immunopathology. In this review, we describe the key players and connections at play in type 2 responses and focus on the emerging mechanisms involved in the negative regulation of type 2 immunity.