P12.05
Background: Recent studies indicate that individuals with low neutrophils (PMN) are at increased risk of HIV infection. Also, the RV144 vaccine trial implicated non-neutralizing antibodies and associated Fc-mediated functions in vaccine-induced protection. These studies suggest that early innate antiviral functions and Fc-mediated functions of PMN may be important mediators of protection. Consequently, protective immunity may rely on kinetics of PMN mobilization, activation, and recruitment during acute HIV/SIV infection.
Methods: We assessed kinetic changes in PMNs in peripheral and mucosal tissues during acute SIV infection in six rhesus macaques challenged i.r. with 100,000 TCID50 of SIVmac239X. Flow cytometry, CBC, and luminex were used to assess PMN and cytokine levels and related PMN functional markers. Samples were collected pre-SIV and days 3, 7, 14, 21, 28, 42, and 63 post-SIV.
Results: We observed a significant decrease in systemic IL-17 (p=.0313) and a trending decrease in G-CSF (p=.0625) early after SIV. Surprisingly, blood PMN concentrations steadily decreased after infection, and no significant increase of PMN was detected in gut tissues. Blood PMN numbers and rectal PMN percentages significantly correlated (p=.0032), and HLA-DR (p=.0313), CD86 (p=.0156), and FcγRI (p=.0313) were significantly upregulated on PMN during acute SIV infection.
Conclusions: In contrast to other acute viral infection models, PMN-supporting cytokines are decreased or not induced during acute SIV, potentially contributing to lack of PMN mobilization from the bone marrow and recruitment to the tissues. Further, blood and rectum PMN levels correlate post-SIV, suggesting that blood PMN concentration may directly impact recruitment to gut tissues. Lastly, upregulation of markers involved in antigen presentation and Fc-mediated functions highlight the potential diverse functional roles of neutrophils during acute SIV infection and the potential importance of inducing neutrophils for effective prevention strategies.
