Transcriptomic profiling of human macrophages infected by Bordetella pertussis.

DENISA PETRÁčKOVÁ; ANA DIENSTBIER; IVO HOFACKER, ; MARIAM FARMAN; IRENA LINHARTOVÁ; JAKUB DR?MÍ?EK, ; FABIAN AMMAN; MARIA EUGENIA RODRIGUEZ ; BRANISLAV VEčEREK

Bruselas

Simposio; 12th International Symposium on Bordetella; 2019

International Bordetella Society

Macrophages represent an important part of the innate immune system as they play several roles in primary responses to pathogens such as B. pertussis. Indeed, majority of B. pertussis cells are killed by macrophages but residual cells evade this killing and survive and replicate inside a nonacidic compartments. Thus, macrophages may provide an intracellular niche permitting bacteria to persist and potentially to spread to new host. In this study we investigated global transcriptomic changes in monocyte-derived macrophages following infection with B. pertussis. This pilot study represents first attempt to assess the global response of human phagocytes to intracellular B. pertussis cells by RNA-seq method. We have applied the dual RNA-seq approach allowing for parallel analysis of transcriptomic profiles in both host and pathogen. Nevertheless, as the numbers of viable intracellular bacteria significantly drop during the infection the focus was put on the host side. Our analysis revealed that gene expression in infected THP-1 macrophages is extensively rewired 6 h post infection. Expression of several cytokine, chemokine and transcription regulator genes that belong to common pattern mounted by host cells upon bacterial infection was highly increased. Interestingly, among the highly expressed genes were also IL-23, IL-1A, CD80 and CD86 which belong to set of genes responsible for induction of M1 macrophage polarization and promoting of Th1 immune response. On the other side, several genes implicated in induction of M2 program in macrophages and mounting of Th2 response were strongly overexpressed upon infection. These results suggest that both pro-inflammatory and anti-inflammatory programs that possibly result from host-pathogen interplay are active in infected cells. Despite limited numbers of bacterial reads we identified several differentially expressed Bordetella genes. Collectively, our preliminary data indicate that intramacrophage phase may play important role in infectious cycle of B. pertussis