Modulation of host immune status by cryptococcus co-infection during HIV-1 pathogenesis and its impact on CD+4 cell and cytokines environment.

Background: Cryptococcus infection is the second most common opportunistic infection in HIV patients with an increased rate of morbidity and mortality. Altered immune system during HIV- Cryptococcus co-infection is yet to be explored by laboratory. This study evaluates pro- and the anti-inflammatory cytokines in HIV patients with Cryptococcus co-infection and correlate them with CD4+T cell counts as well as viral loads before the initiation of drug therapy. This information would enable to understand host immune modulation and cellular environment during co-infection and understand its impact on HIV pathogenesis.

Methodology: The study comprised four categories of patients with cryptococcosis, HIV, HIV-cryptococcosis co-infected and asymptomatic Healthy volunteers. All the patients and healthy individuals were subjected to CD4+T cells count by FACS using monoclonal antibody cocktail CD4+T cell count (counts per mm3) which was counted using multiSET software on FACS caliber. The viral loads were counted in terms of viral RNA copy numbers which was estimated by real-time PCR using by Artus HIV-1 RG. The sensitivity of kit was >70 IU/ml. ELISA was performed for IL-12 p70, IL-12, IL-4, IL-10, IL-6, TNF-α and IFN-Y using commercially kits (BD Biosciences, USA). Significant variations were assayed by Student's t-test and P values ≤ 0.05 were considered statistically significant.

Results: Reduction in CD+4 cell counts was highly significant in HIV patients with or without cryptococcosis. CD4+T cell counts were inversely proportional to viral load. TNF-α levels were raised in cryptococcosis patients significantly higher than healthy individuals. TNF-α was more or less not dependent on viral load but it was more related to the cryptococcosis IL-12 levels were increased in patients with infection and was highest in the HIV infected group. Level of IL-4 was similar in healthy and patients with cryptococcosis but it was elevated in HIV-Crypto co-infected patients. HIV infected patients showed a significant increase in IL-4 level and it was elevated higher in co-infected patients. IL-10 and IL-6 were significantly higher in HIV patients. The fungal infection did not influence the levels of IL-10 in HIV group but IL-6 was low in fungal infected patients.

Conclusion: There are very limited studies related to the immune modulation status of HIV co-infected with Cryptococcus before the initiation of any drug therapy. Such information might through in-depth light to understand the initial state of the immune environment which certainly would play a pivotal role in the outcome of the immune modulation.