Identification of an Increased Alveolar Macrophage Subpopulation in Old Mice That Displays Unique Inflammatory Characteristics and Is Permissive to Mycobacterium tuberculosis Infection

The elderly population is more susceptible to pulmonary infections, including tuberculosis. In this article, we characterize the impact of aging on the phenotype of mouse alveolar macrophages (AMs) and their response to Mycobacterium tuberculosis. Uninfected AMs were isolated from bronchoalveolar lavage of young (3 mo) and old (18 mo) C57BL/6 mice. AMs from old mice expressed higher mRNA levels of CCL2, IFN-beta, IL-10, IL-12p40, TNF-alpha, and MIF than young mice, and old mice contained higher levels of CCL2, IL-1beta, IFN-beta, and MIF in their alveolar lining fluid. We identified two distinct AM subpopulations, a major CD11c(+) CD11b(-) population and a minor CD11c(+) CD11b(+) population; the latter was significantly increased in old mice (4-fold). Expression of CD206, TLR2, CD16/CD32, MHC class II, and CD86 was higher in CD11c(+) CD11b(+) AMs, and these cells expressed monocytic markers Ly6C, CX3CR1, and CD115, suggesting monocytic origin. Sorted CD11c(+) CD11b(+) AMs from old mice expressed higher mRNA levels of CCL2, IL-1beta, and IL-6, whereas CD11c(+) CD11b(-) AMs expressed higher mRNA levels of immune- regulatory cytokines IFN-beta and IL-10. CD11c(+) CD11b(+) AMs phagocytosed significantly more M. tuberculosis, which expressed higher RNA levels of genes required for M. tuberculosis survival. Our studies identify two distinct AM populations in old mice: a resident population and an increased CD11c(+) CD11b(+) AM subpopulation expressing monocytic markers, a unique inflammatory signature, and enhanced M. tuberculosis phagocytosis and survival when compared with resident CD11c(+) CD11b(-) AMs, which are more immune regulatory in nature.