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Accumulation of functionally immature myeloid dendritic cells in lymph nodes of rhesus macaques with acute pathogenic simian immunodeficiency virus infection
Author(s) -
Wijewardana Viskam,
Bouwer Anthea L.,
Brown Kevin N.,
Liu Xiangdong,
BarrattBoyes Simon M.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12295
Subject(s) - simian immunodeficiency virus , lymph , immunology , biology , lymph node , c c chemokine receptor type 7 , innate immune system , virus , virology , immune system , medicine , pathology , chemokine , chemokine receptor
Summary Myeloid dendritic cells ( mDC ) are key mediators of innate and adaptive immunity to virus infection, but the impact of HIV infection on the m DC response, particularly early in acute infection, is ill‐defined. We studied acute pathogenic simian immunodeficiency virus ( SIV ) infection of rhesus macaques to address this question. The m DC in blood and bone marrow were depleted within 12 days of intravenous infection with SIV mac251, associated with a marked proliferative response. In lymph nodes, m DC were apoptotic, activated and proliferating, despite normal m DC numbers, reflecting a regenerative response that compensated for m DC loss. Blood m DC had increased expression of MHC class II , CCR 7 and CD 40, whereas in lymph nodes these markers were significantly decreased, indicating that acute infection induced maturation of m DC in blood but resulted in accumulation of immature m DC in lymph nodes. Following SIV infection, lymph node m DC had an increased capacity to secrete tumour necrosis factor‐ α upon engagement with a T oll‐like receptor 7/8 ligand that mimics exposure to viral RNA , and this was inversely correlated with MHC class II and CCR 7 expression. Lymph node m DC had an increased ability to capture and cleave soluble antigen, confirming their functionally immature state. These data indicate that acute SIV infection results in increased m DC turnover, leading to accumulation in lymph nodes of immature m DC with an increased responsiveness to virus stimulation.