Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination

David Furman1, Boris P. Hejblum2, Noah Simon3, Vladimir Jojic4, Cornelia L. Dekker5, Rodolphe Thiébaut2, Robert Tibshirani6,3, Mark M. Davis1,7,8
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5323.
2ISPED-Epidemiologie-Biostatistique and Institut National de la Santé et de la Recherche Médicale (INSERM), Centre INSERM U897, University of Bordeaux, and INRIA–Statistics in System Biology and Translational Medicine Team, F-33000 Bordeaux, France;
3Department of Statistics, Stanford University, Stanford, CA 94305-4065;
4dDepartment of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3175;
5Department of Pediatrics, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305-5208;
6Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305-5405;
7Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5323
8Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305-5124; and

Tóm tắt

SignificanceThere are marked differences between the sexes in their immune response to infections and vaccination, with females often having significantly higher responses. However, the mechanisms underlying these differences are largely not understood. Using a systems immunology approach, we have identified a cluster of genes involved in lipid metabolism and likely modulated by testosterone that correlates with the higher antibody-neutralizing response to influenza vaccination observed in females. Moreover, males with the highest testosterone levels and expression of related gene signatures exhibited the lowest antibody responses to influenza vaccination. This study generates a number of hypotheses on the sex differences observed in the human immune system and their relationship to mechanisms involved in the antibody response to vaccination.

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