Sex Differences in the Innate Immune Response to Heart-Passaged Coxsackievirus B3: Microarray Analysis (45.16)

Abstract

Recent studies have shown that innate immunity influences the progression from viral infection to autoimmunity. The incidence and severity of autoimmune disease differs between men and women, including the heart inflammatory autoimmune disease myocarditis which is increased in men. To better understand the reason for increased heart disease in men, we studied sex differences in the innate immune response to heart-passaged coxsackievirus B3 (CVB3) in BALB/c mice by microarray. Five male and female BALB/c mice were infected intraperitoneally (ip) with CVB3 and spleens harvested 12 hours (h) later during the innate immune response and compared to uninfected controls. Gene expression was determined using an Affymetrix Mouse Gene 1.0 ST Array. We found that 24 genes were significantly increased in CVB3 infected males vs. females (>1.5 fold change). Androgen receptor (AR) mRNA was significantly decreased in infected males vs. infected females indicating activation of the receptor. Heat shock protein 90 (HSP90) and haptoglobin (Hp) mRNA were significantly increased in infected males vs. infected females. AR, HSP90 and Hp have been associated with increased heart disease in men. Significant gene changes were verified using qRT-PCR. Thus, we found that several genes important for the development of clinical heart disease are upregulated in males during the innate immune response. Funded in part by the Johns Hopkins University Diversity Summer Internship Program and NIH R01 HL087033.