Transcriptome analysis of infected human macrophages between strains of Brucella melitensis and an omp31 mutant

Transcriptome of macrophages infected with B. melitensis

Abstract

Brucella spp. are small aerobes non-motile Gram-negative coccobacilli that act as facultative intracellular pathogens responsible for zoonotic infections. B. melitensis can survive and replicate within host macrophages, the molecular phenomena of this host: pathogen interaction remain totally unknown. The aim of this work was to evaluate the differences in the response between human macrophages infected with different B. melitensis strains. Comparison of transcriptome data was carried out for identifying differentially expressed genes among different strain infection. We evaluated the THP-1 macrophage molecular response at early stages of infection to different strains of Brucella melitensis (B. melitensis wild- type 133 (BM133), B. melitensis ATCC 23456 (BM16M) and a B. melitensis 133 omp31 mutant (LVM31)). Our analysis revealed intriguing differences in the host cell response to two virulent strains (BM16M and BM133), infection with BM16M led to an over-expression of anti-inflammatory pathways, such as cAMP signaling and PI3K-Akt pathway, and down regulation of inflammatory pathways involving IL1A and IL10 compared to BM133. Mutant strain BMLVM31 induced an activation of the apoptotic process and the absence of Omp31, impaired the inhibition of CASP1 and CASP9 expression. Additionally, the mutation of BMLV31 impairs the evasion of cathepsin D in early stages of the infection. These findings shed light on the intricate molecular interactions between B. melitensis strains and human macrophages, providing valuable insights for understanding the pathogenesis of brucellosis.