AUTHOR=Khiter Fethi , Kherrouche Zoulika , Dubois Violaine , Slupek Stéphanie , Petit Emmanuelle , Debrie Anne-Sophie , Cauchi Stéphane , Barois Nicolas , Rouanet Carine , Mielcarek Nathalie 

TITLE=Combined regulation of pro-inflammatory cytokines production by STAT3 and STAT5 in a model of B. pertussis infection of alveolar macrophages

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1254276

DOI=10.3389/fimmu.2023.1254276

ISSN=1664-3224

ABSTRACT=<p><italic>Bordetella pertussis</italic> is a highly contagious respiratory pathogen responsible for whooping-cough or pertussis. Despite high vaccination coverage worldwide, this gram-negative bacterium continues to spread among the population. <italic>B. pertussis</italic> is transmitted by aerosol droplets from an infected individual to a new host and will colonize its upper respiratory tract. Alveolar macrophages (AMs) are effector cells of the innate immune system that phagocytose <italic>B. pertussis</italic> and secrete both pro-inflammatory and antimicrobial mediators in the lungs. However, understanding their role in <italic>B. pertussis</italic> pathogenesis at the molecular level is hampered by the limited number of primary AMs that can be collected <italic>in vivo</italic>. In order to decipher the regulation of innate response induced by <italic>B. pertussis</italic> infection, we used for the first time self-renewing, non-transformed cells, called Max Planck Institute (MPI) cells, which are phenotypically and functionally very close to pulmonary AMs. Using optimized infection conditions, we characterized the entry and the clearance of <italic>B. pertussis</italic> within MPI macrophages. We showed that under these conditions, MPI cells exhibit a pro-inflammatory phenotype with the production of TNF, IL-1β, IL-6 and MIP-2α, similarly to primary AMs purified from broncho-alveolar fluids of mice. In addition, we explored the yet uncharacterized role of the signal transduction activator of transcription (STAT) proteins family in the innate immune response to <italic>B. pertussis</italic> infection and showed for the first time the parallel regulation of pro-inflammatory cytokines by STAT3 and STAT5 in MPI macrophages infected by <italic>B. pertussis</italic>. Altogether, this work highlights the interest of using MPI cells for experiments optimization and preliminary data acquisition to understand <italic>B. pertussis</italic> interaction with AMs, and thus significantly reduce the number of animals to be sacrificed.</p>