An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens

Meliopoulos, Victoria A.; Van de Velde, Lee-Ann; Van de Velde, Nicholas C.; Karlsson, Erik A.; Neale, Geoff; Vogel, Peter; Guy, Cliff; Sharma, Shalini; Duan, Susu; Surman, Sherri L.; Jones, Bart G.; Johnson, Michael D. L.; Bosio, Catharine; Jolly, Lisa; Jenkins, R. Gisli; Hurwitz, Julia L.; Rosch, Jason W.; Sheppard, Dean; Thomas, Paul G.; Murray, Peter J.; Schultz-Cherry, Stacey

Most pulmonary AM originate from embryonic erythro-myeloid progenitors whose replacement by blood monocytes under steady state is extremely slow [42, 44] . To test whether the β6 KO CD11c + CD11b + AM were predominantly derived from embryonic progenitors, we created mice where the blood monocyte pool was severely depleted by loss of the chemokine receptor CCR2, which is the predominant mediator for monocyte egress from the bone marrow. In the lungs of β6/CCR2 doubly-deficient mice, CD11c + CD11b + AM were present in identical amounts compared with those of β6 KO mice, arguing these cells are unlikely to be derived from peripheral blood monocytes (S4C Fig). Although other unknown pathways to recruit monocytes to the lung cannot be discounted, they are not as well characterized or understood as the CCR2 pathway. Taken together, we concluded loss of an epithelial integrin alters the phenotype of lung AMs.