Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection.

Our understanding of innate immune responses in human rectal mucosal tissues (RM) and their contributions to promoting or restricting HIV transmission is limited. We defined the RM composition of innate and innate-like cell subsets, including plasmacytoid dendritic cells; CD1c + myeloid DCs; neutrophils; macrophages; natural killer cells (NK); Marginal Zone-like B cells (MZB); γδ T cells; and mucosal-associated invariant T cells in RM from 69 HIV-negative men by flow cytometry. Associations between these cell subsets and HIV-1 replication in ex vivo RM explant challenge experiments revealed an inverse correlation between RM-NK and p24 production, in contrast to a positive association between RM-MZB and HIV replication.

Author Correction: Distribution of Functional CD4 and CD8 T cell Subsets in Blood and Rectal Mucosal Tissues.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Distribution of Functional CD4 and CD8 T cell Subsets in Blood and Rectal Mucosal Tissues.

A better understanding of the distribution and functional capacity of CD4 T helper (Th) and CD8 T cytotoxic (Tc) cell subsets in the rectal mucosa (RM), a major site for HIV acquisition and replication, in adults is needed. In this study, we compared the distribution of Th and Tc cell subsets between blood and RM compartments in 62 HIV negative men, focusing primarily on IL-17-producing CD4 and CD8 T cells due to their importance in establishing and maintaining mucosal defenses, and examined associations between the frequencies of Th17 and Tc17 cell subsets and the availability of highly HIV-susceptible target cells in the RM. The RM exhibited a distinct immune cell composition comprised of higher frequencies of Th2, Th17, and Tc17 cells compared to the peripheral blood.

In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques.

Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure.

Association of Cytokines With Exosomes in the Plasma of HIV-1-Seropositive Individuals.

Human immunodeficiency virus (HIV)-infected and viremic individuals exhibit elevated levels of plasma cytokines. Here we show that most cytokines are not in free form but appear associated with exosomes that are distinct from virions. Purified exosomes were analyzed to determine the levels of 21 cytokines and chemokines and compared with exosome-depleted plasma.

TIM-3, a Possible Target for Immunotherapy in Cancer and Chronic Viral Infections.

Effector T-cell responses are controlled by complex mechanisms involving various soluble factors and co-stimulatory and co-inhibitory molecules. These inhibitory receptors act as immune checkpoints and are extensively investigated as possible therapeutic targets, such as PD-1 and CTLA-4. Recently TIM-3 is also gaining prominence in tumor and chronic viral infection models as a candidate for immunotherapy in conjunction with other inhibitory receptors.

Characterization of the mannose 6-phosphate receptor (Mr 300 kDa) protein dependent pathway of lysosomal enzyme targeting in Biomphalaria glabrata mollusc cells.

Mammalian mannose 6-phosphate receptors (MPR 300 and 46) are involved in the targeting of newly synthesized lysosomal enzymes and only MPR 300 also participates in the endocytosis of various exogenous ligands. The present study describes for the first time the MPR 300 dependent pathway of lysosomal enzyme sorting in the Biomphalaria glabrata embryonic (Bge) cells. Lysosomal enzymes (arylsulfatase A, beta-hexosaminidase and alpha-fucosidase) were identified by their enzymatic activities and by immunoprecipitation with specific antisera.

Reptilian MPR 300 is also the IGF-IIR: cloning, sequencing and functional characterization of the IGF-II binding domain.

The mammalian cation-independent mannose 6-phosphate/insulin-like growth factor (IGF)-II receptor binds IGF-II with high affinity. Ligands transported by the MPR 300/IGF-IIR include IGF-II and mannose 6-phosphate-modified proteins. By targeting IGF-II to lysosomal degradation, it plays a key role in the maintenance of correct IGF-II levels in the circulation and in target tissues.

Molecular cloning, expression and functional characterization of the chicken cation dependent mannose 6-phosphate receptor protein.

Mammalian mannose 6-phosphate (M6P) receptors function in transport of lysosomal enzymes. To understand the structural and functional significance of the chicken cation dependent mannose 6-phosphate receptor (MPR) (Mr 46 kDa), a full-length cDNA for the chicken protein was cloned and expressed in mpr(-/-) MEF cells devoid of both the receptors. The stably transfected cells express the receptor that could be affinity purified by phosphomannan chromatography.

Biochemical and functional characterization of cation dependent (Mr 46,000) goat mannose 6-phosphate receptor.

The Mannose 6-phosphate receptor (MPR's) proteins are important for transporting lysosomal enzymes from trans-golgi to the pre-lysosomal compartment. These are conserved in the vertebrates from fish to mammals. We have cloned the full length cDNA for the goat MPR 46 protein and compared its sequences to the other known vertebrate MPR 46 proteins.