Macrophage renewal in the small intestine governs early-life control of streptococci

Mansoori Moghadam, Z.; Freudenhammer, M.; Viola, M. F.; Eckert, M.; Raynaud, C.; Kriegl, L.; Rauer, M.; Alsumati, R.; Treichel, N.; Eckert, R. R.; Baasch, S.; Boerries, M.; Mass, E.; Clavel, T.; Erny, D.; Kolter, J.; Henneke, P.

doi:10.64898/2026.02.11.705249

bioRxiv · 10.64898/2026.02.11.705249

Macrophage renewal in the small intestine governs early-life control of streptococci

Mansoori Moghadam, Z.·Freudenhammer, M.·Viola, M. F.·Eckert, M.·Raynaud, C.·Kriegl, L.·Rauer, M.·Alsumati, R.·Treichel, N.·Eckert, R. R.·Baasch, S.·Boerries, M.·Mass, E.·Clavel, T.·Erny, D.·Kolter, J.·Henneke, P.

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Abstract

Group B Streptococcus (GBS) is both a common intestinal colonizer that is transmitted intergenerationally, and a primary cause of neonatal sepsis worldwide. However, the innate immune mechanisms that restrict the pathogen at the intestinal barrier early in life remain poorly understood. Using an enteral GBS-colonization model in infant mice, we found that lamina-propria (LP) macrophages controlled both GBS-colonization densities and invasion in an age-dependent fashion. LP macrophages turnover and differentiation were strongly impacted by topology. In the small intestine, monocytes infiltration of the LP occurred from birth on in response to perinatally acquired microbiota, whereas in the colon it was driven by the weaning reaction. Moreover, macrophages of the small intestine mounted a robust, MyD88-dependent inflammatory response to GBS, while those of the colon remained largely unaffected. Together, these findings demonstrate that region-specific macrophage dynamics early in life critically influence host-pathogen-interactions during GBS-colonization.

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Mansoori Moghadam, Z., Freudenhammer, M., Viola, M. F., Eckert, M., Raynaud, C., Kriegl, L., Rauer, M., Alsumati, R., Treichel, N., Eckert, R. R., Baasch, S., Boerries, M., Mass, E., Clavel, T., Erny, D., Kolter, J., Henneke, P.. 2026-02-12. Macrophage renewal in the small intestine governs early-life control of streptococci. https://doi.org/10.64898/2026.02.11.705249

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