Unraveling Pregnancy-Induced Modulation of the Innate Immune Response to Mycobacterium tuberculosis Through mRNA Sequencing of Infected Monocytes

Abstract

This thesis investigates the dynamics of monocyte-derived macrophage gene expression in response to Mycobacterium tuberculosis (Mtb) infection during pregnancy, focusing specifically on the third trimester. Using mRNA sequencing, we found significant changes in gene expression related to the innate immune response, particularly in the JAK-STAT pathway associated with tuberculosis reactivation. Analysis revealed over 500 differently expressed genes in infected samples, primarily involved in cytokine signaling and inflammation. Comparing third trimester of pregnancy to pre-pregnancy highlighted differences in pathways such as calcium signaling, MAPK, TNF, MTORC, and hypoxia signaling. Downregulated genes like GBP5, TNFRSF4, and NIBAN1 suggest compromised immune response in late pregnancy, potentially worsening TB infection or reactivation of latent TB. Understanding these changes could improve TB prevention, diagnosis, and treatment in pregnant populations.