The Importance of Regulation in Natural Immunity to HIV

Abstract

Worldwide, most Human Immunodeficiency Virus (HIV) infections are acquired through heterosexual intercourse, and in sub-Saharan Africa, 59% of new HIV infections affect women. Vaccines and microbicides hold promise for preventing the acquisition of HIV. To this end, the study of HIV highly exposed seronegative (HESN) female commercial sex workers (CSWs), who constitute a model of natural immunity to HIV, provides an exceptional opportunity to determine important clues for the development of preventive strategies. Studies using both female genital tract (FGT) and peripheral blood samples of HESN CSWs, have allowed identifying distinct features, notably low-inflammatory patterns associated with resistance to infection. How this seemingly regulated response is achieved at the initial site of HIV infection remains unknown. One hypothesis is that populations presenting regulatory profiles contribute to the orchestration of potent anti-viral and low-inflammatory responses at the initial site of HIV transmission. Here, we view to update our knowledge regarding this issue.

Excess BAFF May Impact HIV-1-Specific Antibodies and May Promote Polyclonal Responses Including Those from First-Line Marginal Zone B-Cell Populations

“…Furthermore, since BAFF promotes NOTCH2 expression [7], this molecule is pivotal for the commitment to the MZ B-cell fate [8]. We have reported similar findings for HIV-1-infected Beninese commercial sex workers (CSWs) [9], and Simian Immunodeficiency Virus (SIV)-infected macaques [9], suggesting that excess BAFF and increased frequencies of MZp are a shared trait of HIV-1 infection, not restored via therapy. Moreover, we have shown that people living with HIV (PLHIV) from the Canadian HIV and Aging Cohort Study (CHACS) possess an excess level of BAFF in their blood and concomitant deregulated MZp even after 15 years of therapy.…”

“…The following mouse anti-human conjugated mAbs were used to detect extracellular markers on B-cells: APC Anti-CD19, BB515 Anti-IgM, AlexaFluor700anti-CD27, BV421 Anti-CD10 (BD Biosciences), PerCP-eFluor 710 Anti-CD1c (eBioscience, San Diego, CA, USA). We had two different staining cocktails, each identical except for a variation for the PE slot, i.e., (1) PE-anti-CD21 (BD Bioscience) to verify that the MZp were indeed CD21lo when compared to CD21hi MZ, and (2) to verify gp120 binding by using biotinylated fully glycosylated or mutated gp120 (Biotin rgp120 HIV-1 IIIB, ImmunoDx, Woburn, MA, USA) and subsequent PE-conjugated streptavidin (Streptavidin-PE, BD-Biosciences), in presence or absence of a pre-incubation with mannose (5 µg/mL for 40 min on ice), as previously described [9]. Data acquisition was performed with FACSFortessa (BD-Biosciences) for blood PBMC samples, and LSRIIB (BD-Biosciences) for tonsillar samples.…”

Advances in Engineered Polymer Nanoparticle Tracking Platforms towards Cancer Immunotherapy—Current Status and Future Perspectives

“…The role of polymeric nanoparticles in immune-related events has been investigated to regulate several immunogenic signals via immune checkpoint therapies for balancing the immune system and cellular homeostasis. The commonly used immune checkpoint inhibitors in cancer therapies are designed for inhibiting receptors (e.g., programmed cell death-1 (PD-1) receptor) typically expressed in T-cells and the ligand (e.g., PD-L1) expressed by cancer cells [ 105 , 106 , 107 ]. During immune signaling, the PD-1 of the T-cell would be attracted by the cancer cells, which results in the inactivation of T-cells while promoting the tumor-associated cytokine secretion to down-regulate cancer-relevant immune responses and tumor growth [ 108 ].…”