Respiratory syncytial virus infection in immunocompetent and immunocompromised murine

The purpose of this study is to distinguish respiratory syncytial virus （RSV） infection and immunology between immunocompetent and immunocompromised murine and to explore immune mechanism of RSV infection. At various time points after RSV infection of BALB/c mice and nude mice, pulmonary viral titers were assayed, RSV antigen was tested by direct immunofluorescent assay and immunohistochemistry. Pulmonary mRNA expressions of Toll like receptor （TLR）2 and TLR4 were assayed by RT-PCR. CD4^＋ ceils and CD8 ^＋ ceils in peripheral blood were examined by flow cytometry and plasma total IgE was assayed by ELISA. Leukocytes in bronchoalveolar lavage fluid （BALF） and pulmonary histology were identified to reflect airway inflammation. It was found that RSV titers of both mice peaked on the 3rd day post infection with a much higher level of viral titer in nude mice than in BALB/c mice and a longer viral duration in nude mice （over 9 days post infection） than in BALB/c mice （6 days post infection）. RSV infection induced higher viral antigen expression in nude mice （0.267 ±0.045） than in BALB/c mice （0. 168 ±0.031）. RSV infection enhanced pulmonary TLR4 expression of BALB/c mice （51.96% ±11.34%） and nude mice （48.96% ± 12.35%） compared with each control （34.04% ±10.06% and 32.37% ±9.87% respectively）. CD4^＋ peripheral blood ceils increased in RSV infected BALB/c mice （66.51% ±2.09% ） compared with the control BALB/c mice （51.63% ±5.90%）, and CD4^＋ ceils and CD8^＋ ceils were deficient in nude mice. RSV infection increased plasma total IgE in both mice, and BALB/c mice had a larger amount of IgE on the 7th day post infection （9.02 ng/ml ±2.90 ng/ml） and on the 14th day post infection （12.76 ng/ml ±4.15 ng/ml） than corresponding nude mice （3.72 ng/ml ±1.06 ng/ml and 7.62 ng/ml ±3.08 ng/ml respectively on the 7th and 14th day post infection）. RSV infected nude mice had more severe airway inflammation than infected BALB/c mice. It is concluded that BALB/c mice and nude mice presented similar RSV infectious characteristics. However, infection of nude mice showed higher viral titer with longer duration and more severe airway inflammation, lower level of plasm total IgE and CD4^＋ peripheral blood cells, but the similar pulmonary TLR4 expression with BALB/c mice.

Cutaneous Dengue Virus Inoculation Triggers Strong B Cell Reactions but Contrastingly Poor T Cell Responses

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.