RESUMO
Phagocytosis of extracellular organisms in the alveolar spaces of the lungs represents the first-line of host defense against pulmonary pathogens. Disruption of this process is likely to interfere with the generation of appropriate specific immune responses, and lead to a delayed or inefficient clearance of the pathogen. Pneumocystis carinii, an opportunistic pathogen in immunodeficient individuals, is cleared from the lung by alveolar macrophages. In the absence of specific anti-Pneumocystis antibodies, phagocytosis is dependent on the non-opsonic macrophage mannose receptor (MR). Recent studies have demonstrated that alveolar macrophage MR activity is downregulated in individuals infected with HIV, and that functional MR is shed from the macrophage cell surface. Here we report that P. carinii enhances the formation of soluble MR by macrophages in vitro. Soluble MR was detected in cell-free alveolar fluid from humans infected with HIV and/or P. carinii, but not in alveolar fluid from healthy controls. Soluble MR was found in association with extracellular clumps of P. carinii in the lungs of mice with P. carinii pneumonia, and was associated with P. carinii organisms purified from these mice. When purified P. carinii organisms were incubated with soluble MR-containing supernatants, they were phagocytosed less readily by alveolar macrophages than were control organisms. Our results suggest that P. carinii organisms enhance the shedding of MR from the surface of alveolar macrophages, and that the resultant soluble MR binds to intra-alveolar organisms, thereby interfering with their non-opsonic uptake via the macrophage cell surface MR.
Assuntos
Lectinas Tipo C , Macrófagos Alveolares/metabolismo , Lectinas de Ligação a Manose , Pneumocystis/patogenicidade , Pneumonia por Pneumocystis/microbiologia , Receptores de Superfície Celular/metabolismo , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/metabolismo , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Animais , Líquido da Lavagem Broncoalveolar/química , Linhagem Celular , Infecções por HIV/metabolismo , HIV-1 , Humanos , Pulmão/microbiologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Receptor de Manose , Camundongos , Camundongos SCID , Fagocitose , Pneumocystis/imunologia , Pneumocystis/metabolismo , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/metabolismo , SolubilidadeAssuntos
Androstadienos/efeitos adversos , Broncodilatadores/efeitos adversos , Doenças da Coroide/induzido quimicamente , Doenças Retinianas/induzido quimicamente , Adulto , Espasmo Brônquico/tratamento farmacológico , Feminino , Fluticasona , Humanos , Parassimpatolíticos/efeitos adversos , Pneumonia por Mycoplasma/complicaçõesRESUMO
Levels of the serum opsonin mannan-binding lectin (MBL) were directly correlated with the probability of developing visceral leishmaniasis. Monocytes infected with MBL-opsonized Leishmania chagasi promastigotes secreted higher levels of tumor necrosis factor alpha and interleukin-6 than cells infected with nonopsonized parasites. Our findings indicate that MBL can modulate the clinical outcome of infection with L. chagasi and the function of infected macrophages.