Impact of a β-lactam on neutrophil in Streptococcus pneumoniae pneumonia ; Impact d'une β-lactamine sur les neutrophiles au cours de la pneumonie à Streptococcus pneumoniae

Pneumococcus, also known as Streptococcus pneumoniae, is a major public health problem as the leading cause of death from acute community-acquired pneumonia worldwide. The first-line treatment for this infection involves the use of β-lactams, antibiotics with bactericidal properties. Interestingly, the literature strongly supports the hypothesis of an interaction between these antibiotics and the host immune system. Indeed, treatment with β-lactam antibiotics leads to the release of microbial molecules that could trigger the activation of components of innate immunity. Among these, neutrophils represent an ideal target given their crucial role in anti-infectious responses, particularly during S. pneumoniae infection.The aim of my thesis was to study the impact of treatment with amoxicillin, a β-lactam commonly used as first-line treatment, on neutrophils during S. pneumoniae infection.To do this, we (i) set up a mouse model of pneumonia secondary to influenza virus infection and (ii) determined an effective dose of amoxicillin. Treatment with amoxicillin led 12 hours after its administration to clearance of the bacteria in superinfected animals, a reduction in the inflammatory response and neutrophil recruitment in the lungs and blood compared with untreated animals. In contrast, when we examined the bone marrow, amoxicillin treatment had no impact on the number of neutrophil progenitors and was accompanied by an increase in the number of mature neutrophils. Transcriptomic and proteomic analyses of mature bone marrow neutrophils showed significant differences, characterized by a reduction in the expression of inflammatory genes (Mmp8, S100a8, Lcn2) and genes (Nos2, Qsox1) and proteins (NCF4, SOD1) associated with oxidative stress after treatment. Studies of the surface markers CD11b, CD62L and CXCR2, as well as functional studies, confirmed the less activated profile of mature neutrophils from treated mice. However, these mature neutrophils conditioned with amoxicillin retained their ability to migrate to the ...