Lactation Remodels the Maternal Lung to Promote Preemptive Innate Defense

Cafiero, T. R.; Lee, S. C.; Huang, C.; Antunes Fernandes, K. H.; Shivarathri, R.; Setiawan, D.; Sen, H.; Ribeiro de Souza, J.; Ye, L.; Mallarino, R.; Krienen, F. M.; Desai, J. V.; Lim, A. I.

doi:10.64898/2026.10.02.756233

bioRxiv · 10.64898/2026.10.02.756233

Lactation Remodels the Maternal Lung to Promote Preemptive Innate Defense

Cafiero, T. R.·Lee, S. C.·Huang, C.·Antunes Fernandes, K. H.·Shivarathri, R.·Setiawan, D.·Sen, H.·Ribeiro de Souza, J.·Ye, L.·Mallarino, R.·Krienen, F. M.·Desai, J. V.·Lim, A. I.

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Abstract

Lactation is a hallmark of mammalian evolution, imposing extraordinary physiological demands on mothers to nourish their offspring. Yet how mothers maintain their own health while meeting these demands remains poorly understood. Here, we discover that lactation establishes a preemptive innate defense program in the maternal lung through enhanced epithelial production of surfactant proteins and mucin, vascular remodeling that supports granulocyte recruitment and accumulation of activated intravascular neutrophils. These tissue-wide adaptations safeguard lactating dams against diverse respiratory pathogens. We further identify prolactin and CGRP as neuroendocrine signals contributing to pulmonary remodeling and uncover parallel lactation-associated granulocyte adaptations in marsupial and non-human primate models. Together, our findings expand the framework of reproductive immunology, revealing that reproduction couples systemic fetal tolerance with tissue-specific immune adaptations that safeguard maternal health during lactation.

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Cafiero, T. R., Lee, S. C., Huang, C., Antunes Fernandes, K. H., Shivarathri, R., Setiawan, D., Sen, H., Ribeiro de Souza, J., Ye, L., Mallarino, R., Krienen, F. M., Desai, J. V., Lim, A. I.. 2026-10-08. Lactation Remodels the Maternal Lung to Promote Preemptive Innate Defense. https://doi.org/10.64898/2026.10.02.756233

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