RESUMO
Inflammation generally leads to recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages is unclear. Here, we show that macrophages elicited into the peritoneal cavity during mild inflammation persist long-term but are retained in an immature transitory state of differentiation due to the presence of enduring resident macrophages. By contrast, severe inflammation results in ablation of resident macrophages and a protracted phase wherein the cavity is incapable of sustaining a resident phenotype, yet ultimately elicited cells acquire a mature resident identity. These macrophages also have transcriptionally and functionally divergent features that result from inflammation-driven alterations to the peritoneal cavity micro-environment and, to a lesser extent, effects of origin and time-of-residency. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages seems to be regulated by the environment.
Assuntos
Diferenciação Celular/genética , Inflamação/genética , Macrófagos Peritoneais/metabolismo , Macrófagos/metabolismo , Cavidade Peritoneal/patologia , Animais , Células Cultivadas , Citocinas/metabolismo , Feminino , Fator de Transcrição GATA6/genética , Fator de Transcrição GATA6/metabolismo , Perfilação da Expressão Gênica , Inflamação/metabolismo , Macrófagos/citologia , Macrófagos Peritoneais/citologia , Masculino , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Peritonite/genética , Peritonite/metabolismoRESUMO
The host response to infection requires an immune response to be strong enough to control the pathogen but also restrained, to minimize immune-mediated pathology. The conflicting pressures of immune activation and immune suppression are particularly apparent in parasite infections, where co-evolution of host and pathogen has selected many different compromises between protection and pathology. Cytokine signals are critical determinants of both protective immunity and immunopathology, and, in this review, we focus on the regulatory cytokine IL-10 and its role in protozoan and helminth infections. We discuss the sources and targets of IL-10 during parasite infection, the signals that initiate and reinforce its action, and its impact on the invading parasite, on the host tissue, and on coincident immune responses.
Assuntos
Helmintíase/imunologia , Interleucina-10/imunologia , Infecções por Protozoários/imunologia , Animais , Citocinas/imunologia , Helmintíase/parasitologia , Interações Hospedeiro-Parasita , Humanos , Parasitos/classificação , Parasitos/fisiologia , Infecções por Protozoários/parasitologiaRESUMO
A 1.6-kb tandem repeat sequence had previously been identified in the subtelomeric region of mini- and megabase chromosomes from Leishmania braziliensis. Southern hybridisation was used to demonstrate that the repeat is complex specific. The sequence was characterised in strains representing four species of the L. braziliensis complex. This data allowed an assessment of the evolutionary relationship of the four species. PCR primers targeted to the repeat amplify only DNA from species of the L. braziliensis complex. Titration assays indicate that a minimum of 50 fg of parasite DNA can be detected by PCR alone. Southern hybridisation increases the limit of detection to 5 fg. Interspecies variation in the repeat sequence enabled restriction enzyme digestion of PCR products to distinguish individual species within the L. braziliensis complex.