Abstract
The mechanisms involved in resistance to HIV-1 infection, especially the role of innate immune response, have not been thoroughly explored in individuals who are repeatedly exposed to HIV-1, but do not get the infection, termed as Exposed sero-negative or ESN. Frequency and activation state of natural killer (NK) cells and plasmacytoid dendritic cells (pDC) in ESNs from North India were compared with those in recently infected HIV positives (RHIV), chronically infected HIV positives (HIV+) and healthy controls (HC). The activation state of NK cells in terms of cytokine response (IFNγ & TNFα) was significantly higher in ESNs compared to the healthy controls, recently infected HIV+ and chronically infected HIV+. Although the number of circulating pDC in different study groups was not significantly different, yet these cells seem to have significantly higher activation state in terms of IFNα production (ex-vivo in response to CpG ODN) in ESNs when compared with other groups. Increased activation status of NK cells and pDC in Exposed but Seronegative individuals indicates their continuous stimulation with HIV antigens due to regular exposure with infected partners and which might be imparting resistance to viral infection in these individuals.
Highlights
Over almost 3 decades since it was first identified, the Human immunodeficiency virus (HIV)/AIDS epidemic has already caused an estimated 25 million deaths worldwide [1]
Spearman’s correlation analysis revealed no significant correlation between percentage of IFNγ producing natural killer (NK) cells and CD4 cell counts in the patient groups (Figure 2(d)) or CD4 counts vs % TNFα positive NK cells (Figure 2(f)). These findings suggest that the enhanced capability of NK cells from exposed seronegative (ESN) to produce IFNγ and TNFα could be associated with natural resistance to HIV-1 infection in these individuals, which need to be demonstrated through a further study on larger number of individuals
Several genetic and adaptive immune mechanisms of natural resistance have been reported in both ESN and long-term nonprogressors (LTNP) [18,19,20,21,22,23,24]. These mechanisms only partially explain the phenomenon of natural resistance observed in some individuals exposed to HIV-1
Summary
Over almost 3 decades since it was first identified, the HIV/AIDS epidemic has already caused an estimated 25 million deaths worldwide [1]. We do understand that not all individuals who are repeatedly exposed to HIV-1 show evidence of infection, sero-conversion and development of disease. Quite apart from those who seroconvert but progress slowly to AIDS (i.e., slow progressors, long-term non-progressors, elite controllers), this rare category of exposed seronegative (ESN) individuals, either resist infection or harbour extremely low levels of virus. The correlates of protection that confer this unique status to a minority of HIV-exposed individuals remain a subject of intense interest, as no single genetic or immunologic parameter has yet been able to fully explain this phenomenon. Studying the disease profile in these individuals in more details may provide invaluable information that will aid in the design of newer vaccines and therapeutic approaches [2,3]
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