RESUMO
Aedes aegypti mosquitoes are vectors for arboviruses of medical importance such as dengue (DENV) and Zika (ZIKV) viruses. Different innate immune pathways contribute to the control of arboviruses in the mosquito vector including RNA interference, Toll and Jak-STAT pathways. However, the role of cellular responses mediated by circulating macrophage-like cells known as hemocytes remains unclear. Here we show that hemocytes are recruited to the midgut of Ae. aegypti mosquitoes in response to DENV or ZIKV. Blockade of the phagocytic function of hemocytes using latex beads induced increased accumulation of hemocytes in the midgut and a reduction in virus infection levels in this organ. In contrast, inhibition of phagocytosis by hemocytes led to increased systemic dissemination and replication of DENV and ZIKV. Hence, our work reveals a dual role for hemocytes in Ae. aegypti mosquitoes, whereby phagocytosis is not required to control viral infection in the midgut but is essential to restrict systemic dissemination. Further understanding of the mechanism behind this duality could help the design of vector-based strategies to prevent transmission of arboviruses.
Assuntos
Aedes/citologia , Aedes/virologia , Vírus da Dengue/fisiologia , Hemócitos/imunologia , Hemócitos/virologia , Zika virus/fisiologia , Aedes/anatomia & histologia , Animais , Feminino , Hemócitos/fisiologia , Mosquitos Vetores , Fagócitos/virologia , FagocitoseRESUMO
Mononuclear phagocytes (MP; monocytes, tissue macrophages, and dendritic cells) are reservoirs, vehicles of dissemination, and targets for persistent HIV infection. However, not all MP population equally support viral growth. Such differential replication is typified by the greater ability of placental macrophages (PM), as compared to blood borne monocyte-derived macrophages (MDM), to restrict viral replication. Since cytosolic protein patterns can differentiate macrophage subtypes, we used a proteomics approach consisting of surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF), tandem mass spectrometry, and Western blots to identify differences between the uninfected and HIV-infected PM and MDM protein profiles linked to viral growth. We performed proteome analysis of PM in the molecular range of 5-20kDa. We found that a SELDI-TOF protein peak with an m/z of 11,100, which was significantly lower in uninfected and HIV-infected PM than in MDM, was identified as cystatin B (CSTB). Studies of siRNA against CSTB treatment in MDM associated its expression with HIV replication. These data demonstrate that the low molecular weight placental macrophage cytosolic proteins are differentially expressed in HIV-infected PM and MDM and identify a potential role for CSTB in HIV replication. This work also serves to elucidate a mechanism by which the placenta protects the fetus from HIV transmission.
Assuntos
Cistatina B/metabolismo , Infecções por HIV/imunologia , HIV-1/crescimento & desenvolvimento , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/virologia , Proteômica , Células Cultivadas , Feminino , Infecções por HIV/metabolismo , Infecções por HIV/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas , Macrófagos Peritoneais/citologia , Fagócitos/citologia , Fagócitos/enzimologia , Fagócitos/virologia , Placenta/imunologia , Placenta/virologia , Gravidez , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Replicação Viral/imunologiaRESUMO
Rotaviruses and reoviruses are involved in human and animal diseases. It is known that both viruses penetrate the gastrointestinal tract but their interaction with phagocytic cells is unknown. To study this interaction, peritoneal resident phagocytic cells were used and rotavirus and reovirus replication in peritoneal phagocytic cells was observed. However, rotavirus replication in these cells led to the production of defective particles since MA-104 cells inoculated with rotavirus phagocytic cell lysate did not show any evidence of virus replication. On the basis of these results, we suggest that, although reovirus dissemination may be helped by these phagocytic cells, these cells may control rotavirus infection and probably contribute to the prevention of its dissemination.