Early immune responses accompanying human asymptomatic Ebola infections

E Leroy

S Baize

P Debre

J Lansoud-Soukate

E Mavoungou

Centre International de Recherches Médicales de Franceville, BP 769, Franceville, Gabon, France

^{Laboratoire Central d'Immunologie cellulaire et tissulaire, Centre National pour la Recherche Scientifique (CNRS), Unité U625, Hôpital Pitié-Salpétrière, Paris, France}

Correspondence: E.M. Leroy, Centre International de Recherches Médicales de Franceville, BP 769, Franceville, Gabon. E-mail: ag.ics.fmric@yorel or rf.oodanaw@eziabniavlys

^{These authors contributed equally to this work}

Centre International de Recherches Médicales de Franceville, BP 769, Franceville, Gabon, France

Accepted 2001 Jan 16.

Abstract

In a recent study we identified certain asymptomatic individuals infected by Ebola virus (EBOV) who mounted specific IgG and early and strong inflammatory 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 composed by soluble antagonist IL-1RA, circulating TNF receptors, IL-10 and cortisol. 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) was up-regulated, strongly suggesting T-cell activation. This T-cell activation was followed by EBOV-specific IgG responses (mainly IgG3 ang IgG1), and by marked and sustained up-regulation of IFNγ, FasL and perforin mRNA expression, suggesting activation of cytotoxic cells. The terminal down-regulation 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. Finally, RT-PCR analysis of TCR-Vβ repertoire usage showed that TCR-Vβ12 mRNA was never expressed during the infection. Taken together, these findings improve our understanding about immune response during human asymptomatic Ebola infection, and throw new light on protection against Ebola virus.

Keywords: Ebola, asymptomatic, immunity, cytokine, TCR

Abstract

Acknowledgments

We thank T. G. Ksiazek and P. E. Rollin (Special Pathogens Branch, CDC, Atlanta, GA, USA) for providing Ebola-specific reagents. We also thank Doctors Pendy, Obiang and Pambo for providing access to their patients. Finally, we thank Doctor Tevi-Benissan, Paul Tshipamba and Issa Bedjebaga for their assistance with the fieldwork. We also thank David Young for correcting the manuscript. CIRMF is supported by the State of Gabon, ELF-Gabon and the Ministère de la Coopération Française.

Acknowledgments

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