Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection

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To determine whether ongoing cell traffic is required for SIV-associated tissue damage, we blocked monocyte and T lymphocyte traffic to the brain and gut during a) ongoing infection or, b) at the time of infection. When animals were treated at four weeks post infection (late), once significant neuronal injury and accumulation of infected macrophages had already occurred, neuronal injury was stabilized, and CNS infection and the number of CNS lesions decreased. In the gut, there were significantly fewer productively infected cells and decreased inflammatory macrophages post treatment. Treatment at the time of infection (early) blocked infection of the CNS (SIV –DNA, RNA, or protein) and macrophage accumulation. In the gut, treatment at the time of infection blocked productive infection (SIV –RNA and protein) but not SIV –DNA. Interestingly, with treatment at the time of infection, there was no evidence of microbial translocation or elevated sCD163 in plasma, demonstrating that leukocyte traffic early plays a role in damage to gut tissues. Overall, these data point to the role of monocyte traffic and possibly lymphocytes to the CNS and leukocyte traffic to the gut to establish and maintain viral reservoirs. They underscore the role of monocyte/macrophage traffic and accumulation in the CNS for neuronal injury and maintenance of CNS lesions.

Vyšlo v časopise: Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004533
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004533

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