Dengue is a global health problem without current specific treatment nor safe vaccines available.While severe dengue is related to pre-existing non-neutralizing dengue virus(DENV)antibodies,the role of T cells in prot...Dengue is a global health problem without current specific treatment nor safe vaccines available.While severe dengue is related to pre-existing non-neutralizing dengue virus(DENV)antibodies,the role of T cells in protection or pathology is unclear.Using cutaneous DENV infection in immunocompetent mice we previously showed the generation of PNA+germinal centers(GCs),now we assessed the activation and proliferation of B and T cells in draining lymph nodes(DLNs).We found a drastic remodelling of DLN compartments from 7 to 14 days post-infection(dpi)with greatly enlarged B cell follicles,occupying almost half of the DLN area compared to*24%in na?ve conditions.Enormous clusters of proliferating(Ki-67+)cells inside B follicles were found 14 dpi,representing*33%of B cells in DLNs but only*2%in noninfected mice.Inside GCs,we noticed an important recruitment of tingle body macrophages removing apoptotic cells.In contrast,the percentage of paracortex area and total T cells decreased by 14–16 dpi,compared to controls.Scattered randomly distributed Ki-67+T cells were found,similar to non-infected mice.CD69 expression by CD4+and CD8+T cells was minor,while it was remarkable in B cells,representing 1764.7%of change from basal levels 3 dpi.The apparent lack of T cell responses cannot be attributed to apoptosis since no significant differences were observed compared to noninfected mice.This study shows massive B cell activation and proliferation in DLNs upon DENV infection.In contrast,we found very poor,almost absent CD4+and CD8+T cell responses.展开更多
基金supported by a grant from CONACYT-Mexico(221102)to Leopoldo Flores-Romoby a CINVESTAV grant to Leticia Cedillo-Barrón
文摘Dengue is a global health problem without current specific treatment nor safe vaccines available.While severe dengue is related to pre-existing non-neutralizing dengue virus(DENV)antibodies,the role of T cells in protection or pathology is unclear.Using cutaneous DENV infection in immunocompetent mice we previously showed the generation of PNA+germinal centers(GCs),now we assessed the activation and proliferation of B and T cells in draining lymph nodes(DLNs).We found a drastic remodelling of DLN compartments from 7 to 14 days post-infection(dpi)with greatly enlarged B cell follicles,occupying almost half of the DLN area compared to*24%in na?ve conditions.Enormous clusters of proliferating(Ki-67+)cells inside B follicles were found 14 dpi,representing*33%of B cells in DLNs but only*2%in noninfected mice.Inside GCs,we noticed an important recruitment of tingle body macrophages removing apoptotic cells.In contrast,the percentage of paracortex area and total T cells decreased by 14–16 dpi,compared to controls.Scattered randomly distributed Ki-67+T cells were found,similar to non-infected mice.CD69 expression by CD4+and CD8+T cells was minor,while it was remarkable in B cells,representing 1764.7%of change from basal levels 3 dpi.The apparent lack of T cell responses cannot be attributed to apoptosis since no significant differences were observed compared to noninfected mice.This study shows massive B cell activation and proliferation in DLNs upon DENV infection.In contrast,we found very poor,almost absent CD4+and CD8+T cell responses.