RESUMO
Pulmonary hypertension (PH) is a disease of diverse etiology. Although primary PH can develop in the absence of prior disease, PH more commonly develops in conjunction with other pulmonary pathologies. We previously reported a mouse model in which PH occurs as a sequela of Pneumocystis infection in the context of transient CD4 depletion. Here, we report that instead of the expected Th2 pathways, the Th1 cytokine IFN-γ is essential for the development of PH, as wild-type mice developed PH but IFN-γ knockout mice did not. Because gene expression analysis showed few strain differences that were not immune-function related, we focused on those responses as potential pathologic mechanisms. In addition to dependence on IFN-γ, we found that when CD4 cells were continuously depleted, but infection was limited by antibiotic treatment, PH did not occur, confirming that CD4 T cells are required for PH development. Also, although CD8 T-cells are implicated in the pathology of Pneumocystis pneumonia, they did not have a role in the onset of PH. Finally, we found differences in immune cell phenotypes that correlated with PH, including elevated CD204 expression in lung CD11c(+) cells, but their role remains unclear. Overall, we demonstrate that a transient, localized, immune response requiring IFN-γ and CD4-T cells can disrupt pulmonary vascular function and promote lingering PH.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/microbiologia , Interferon gama/metabolismo , Pneumocystis/fisiologia , Animais , Líquido da Lavagem Broncoalveolar , Fibrose , Regulação da Expressão Gênica , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/patologia , Imunidade/genética , Imunofenotipagem , Interleucina-12/metabolismo , Depleção Linfocítica , Camundongos , Camundongos Knockout , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/genética , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/patologia , Fator de Transcrição STAT6/deficiência , Fator de Transcrição STAT6/metabolismo , Receptores Depuradores Classe A/metabolismo , Regulação para CimaRESUMO
We investigated the intestinal parasites of a wild fish population in a Kansas stream to determine the prevalence and abundance of potentially harmful parasites. In total, 180 red shiners (Cyprinella lutrensis) were collected from 6 sites in October-November 2007. Fifteen Asian tapeworms (Bothriocephalus acheilognathi) were recovered from 13 fish (prevalence of 7.2%). Prevalence did not differ among sites; however, B. acheilognathi abundance was greatest at the site of a public fishing area. A total of 39 roundworms (Rhabdochona canadensis) were recovered from 28 fish (prevalence of 15.6%). Prevalence did not differ among sites, nor did abundance. However, mean abundance tended to be about 50% greater at the site of a public fishing area compared to all other sites. This paper documents the presence of both B. acheilognathi and R. canadensis in Kansas and offers a compilation of the known potential impacts these parasites may have on the native, federally endangered Topeka shiner (Notropis topeka).