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Subsets of CD16-positive monocytes produce proinflammatory cytokines and expand during chronic infection with the human immunodeficiency virus type 1 (HIV). HIV-infected macrophage in tissues may be long lived and contribute to the establishment and maintenance of the HIV reservoir. We found that the (intermediate) CD14++CD16+ and (nonclassical) CD14+CD16++ monocyte subsets are significantly expanded during infection of Rhesus macaques with pathogenic SIVmac251 but not during infection of sooty mangabeys with the nonpathogenic isolate SIVSM. In vitro glucocorticoid (GC) treatment of peripheral blood mononuclear cells (PBMCs) from uninfected or SIVmac251-infected Rhesus macaques and HIV-infected patients treated or not with antiretroviral therapy (ART) resulted in a significant decrease in the frequency of both CD16-positive monocyte subsets. Short-term in vivo treatment with high doses of GC of chronically SIVmac251-infected macaques resulted in a significant decrease in the CD14+CD16++ population and, to a lesser extent, in the CD14++CD16+ monocytes, as well as a significant decrease in the number of macrophages in tissues. Surprisingly, treatment of SIVmac251-infected macaques with ART significantly increased the CD14++CD16+ population and the addition of GC resulted in a significant decrease in only the CD14+CD16++ subset. No difference in SIV DNA levels in blood, lymph nodes, gut, and spleen was found between the groups treated with ART or ART plus GC. Thus, it appears that high doses of GC treatment in the absence of ART could affect both CD16-positive populations in vivo. Whether the efficacy of this treatment at higher doses to decrease virus levels outweighs its risks remains to be determined. [ABSTRACT FROM AUTHOR]

BackgroundLymph nodes (LNs) are important sites of connection between the sampled peripheral tissues, the many cells of the immune system, and the blood. The organization of the interface between the afferent and efferent lymphatic vasculature and LN parenchyma is incompletely understood, and obtaining a better understanding of these tissue microenvironments will contribute to an improved understanding of overall lymphatic function. Methods and ResultsWe used histologic approaches to define the distributions of cells expressing lymphatic endothelial cell (LEC) markers in LNs from healthy, simian immunodeficiency virus (SIV) infected, or Mycobacterium tuberculosisinfected cynomolgus macaques. Cells at the afferent and efferent interfaces of LNs from all animals showed differential expression of LEC markers, with podoplanin, Prox-1, and VEGFR3 expressed in both microenvironments, but with LYVE-1 expressed only at the efferent interface. The chemokine CCL20 was uniquely expressed at the afferent interface by cells co-expressing podoplanin, and this expression was increased during SIV or M. tuberculosisinfection. In contrast, only a small proportion of cells expressing the CCR7 ligand CCL21 co-expressed podoplanin. Treatment of model LECs with the TLR3 ligand poly(IC) or γ-irradiated M. tuberculosisincreased production of CCL20 without altering CCL21 or LEC marker expression. ConclusionsThis study provides a comprehensive mapping of the organization of the lymphatic endothelial network entering and exiting LNs in health and in chronic infectious diseases in a nonhuman primate model. The differences we have defined between the afferent and efferent interfaces of LNs could inform the future design of vaccines and immunotherapies. [ABSTRACT FROM AUTHOR]

An abstract of the article "Adjuvant Dependent Mucosal V2 Responses and RAS Activation in Vaccine Induced Protection from SIV mac251 Acquisition" by Monica Vaccari, Shari N. Gordon, Slim Fourati and colleagues is presented.

An abstract of the article "Do CD16+NKG2A+NK Cells Recruited to the Gut Combined with Passively Administered SIV Specific Antibodies Prevent SIVmac251 Acquisition in Macaques?" by Namal P. M. Liyanage, Melvin N. Doster and colleagues is presented.

An abstract of the article "Modulation of RAS Pathways as a Biomarker of Protection against HIV and as a Means to Improve Vaccine Efficacy" by Slim Fourati, Monica Vaccari, Shari N. Gordon and colleagues is presented.

An abstract of the article "Plasmablast Phenotype and Mucosal Antibodies to V2 in Vaccine-induced Protection Against SIVmac251" by Luca Schifanella, Nicolo Binello, Monica Vaccari and colleagues is presented.