biostudies-literatureUnknownEarhart APNHLBI NIH HHSNCI NIH HHSComplement protein C3 is crucial for immune responses in mucosal sites such as the lung, where it aids in microbe elimination and enhances inflammation. While trained immunity - enhanced secondary responses of innate immune cells after prior exposure - is well-studied, the role of the complement system in trained immune responses remains unclear. We investigated the role of C3 in trained immunity and found that <i>in vivo</i>, trained wild-type mice showed significantly elevated pro-inflammatory cytokines and increased C3a levels upon a second stimulus, whereas C3-deficient mice exhibited a blunted cytokine response and heightened evidence of lung injury. <i>Ex vivo</i>, C3-deficient alveolar macrophages (AMs) displayed reduced chemokine and cytokine output after training, which was restorbioRxiv : the preprint server for biology2024.11.01.621042https://www.ebi.ac.uk/biostudies/studies/S-EPMC11565986biostudies-literatureThe C3-C3aR axis modulates trained immunity in alveolar macrophages.PMC11565986P30 CA091842T32 HL125241R01 HL169860Garnica LKulkarni HSEarhart APNallapu AHaspel JAOzanturk ANAlburquerque RAMaurya RKStarick MWu XfalseThe C3-C3aR axis modulates trained immunity in alveolar macrophages.Complement protein C3 is crucial for immune responses in mucosal sites such as the lung, where it aids in microbe elimination and enhances inflammation. While trained immunity - enhanced secondary responses of innate immune cells after prior exposure - is well-studied, the role of the complement system in trained immune responses remains unclear. We investigated the role of C3 in trained immunity and found that <i>in vivo</i>, trained wild-type mice showed significantly elevated pro-inflammatory cytokines and increased C3a levels upon a second stimulus, whereas C3-deficient mice exhibited a blunted cytokine response and heightened evidence of lung injury. <i>Ex vivo</i>, C3-deficient alveolar macrophages (AMs) displayed reduced chemokine and cytokine output after training, which was restor2024-01-01T00:00:00Z2024 Nov2025-04-04T02:12:24.606Z2025-04-04T02:12:24.606ZS-EPMC115659863955400010.1101/2024.11.01.621042