As we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF–exposed Mtb had reduced control and fewer phagosome–lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.

Chlamydia trachomatis is the most commonly reported bacterial sexually transmitted infection in the United States. Modeling infection in animals can be challenging, as mice naturally clear C. trachomatis when it is deposited in the lower genital tract. However, C. trachomatis can productively infect mice when the lower genital tract is bypassed and bacteria are deposited directly into the upper genital tract via transcervical inoculation. Interestingly, the mouse-adapted Chlamydia species C. muridarum can infect mice both by transcervical inoculation and by natural ascension if introduced into the vaginal vault. In this study, we investigated whether the route of infection plays a role in the downstream immune responses to C. muridarum infection. We found that transcervical infection with C. muridarum results in higher bacterial burdens in the upper genital tract at earlier time points, correlating with levels of innate immune cells. When bacterial burdens were equivalent in intravaginally and transcervically infected mice at later time points, we observed substantially higher levels of adaptive immune cells in transcervically infected mice. Our data suggest that different routes of infection with the same organism can elicit different immune responses in the same tissue.

In recent years, the incidence of HIV has decreased, however it continues to spread globally. 70-90% of individuals infected with HIV develop oral mucosal infections. Interestingly, HIV infected patients are at higher risk of developing Epstein–Barr virus (EBV)-associated B cell malignancies in tonsils. However, the potential role of oral immunity in pathogenesis of oral lesions is unknown. Tonsils are considered oral-pharyngeal mucosal associated lymphoid tissues and play an important role in oral mucosal immunity. However, detailed study of human tonsillar immune cells during HIV infection is restricted due to limited sample availability. In this study, we investigated the role of innate and adaptive immune cells in macaque tonsils by high dimensional flow cytometry analysis. Our data revealed a novel innate B cell subset that express NK cell receptors (NKB) significantly increased during SIV chronic infection in tonsils. We also found loss of ploy functional memory CD8 T cells during SIV infections. Tonsillar IL17 producing Cytotoxic T cells (Tc17+) were significantly increased during infection despite a loss in Th17 cells. Consistent with our previous studies in gut mucosal tissues, we found a significant loss of NCR+ILC3 in the tonsils during SIV infection. However, in contrast to the gut, we observed an expansion of oral CD56+ NK cells in tonsils during chronic SIV infection. These data suggest that the SIV associated immune responses are significantly distinct in the tonsils compared to other mucosal tissues. These data extend our understanding of the oral innate immune system during SIV infection and could aid future studies in evaluating the role of tonsillar immune cells during HIV associated oral mucosal infections.