Early immune responses accompanying human asymptomatic Ebola infections

In a recent study we identified certain asymptomatic individuals infected b y Ebola virus (EBOV) who mounted specific IgG and early and strong inflamma tory responses. Here, we further characterized the primary immune response to EBOV during the course of asymptomatic infection in humans. Inflammatory responses occurred in temporal association with anti-inflammatory phase co mposed by soluble antagonist IL-1RA, circulating TNF receptors, IL-10 and c ortisol. At the end of the inflammatory process, mRNA expression of T-cell cytokines (IL-2 and IL-4) and activation markers (CD28, CD40L and CTLA4) wa s up-regulated, strongly suggesting T-cell activation. This T-cell activati on was followed by EBOV-specific IgG responses (mainly IgG3 ang IgG1), and by marked and sustained up-regulation of IFN gamma, FasL and perforin mRNA expression, suggesting activation of cytotoxic cells. The terminal down-reg ulation of these latter markers coincided with the release of the apoptotic marker 41/7 NMP in blood and with the disappearance of viral RNA from PBMC , suggesting that infected cells are eliminated by cytotoxic mechanisms. Fi nally, RT-PCR analysis of TCR-V beta repertoire usage showed that TCR-V bet a 12 mRNA was never expressed during the infection. Taken together, these f indings improve our understanding about immune response during human asympt omatic Ebola infection, and throw new light on protection against Ebola vir us.