Mycobacterium tuberculosis manipulates pulmonary APCs subverting early immune responses

Abstract

Alveolar macrophages (AM) and dendritic cells (DCs) are the main antigen presenting cells (APCs) in the respiratory tract. Whereas macrophages have been extensively studied in tuberculosis, in situ interactions of DC with Mycobacterium tuberculosis (Mtb) are poorly explored. We aimed to characterize lung APCs during pulmonary tuberculosis in Balb/C mice infected with Mtb H37Rv. Mtb-infection via the airways induced a delayed and continuous accumulation of DCs and AM in the lungs. While lung DCs increased after day 3 post-infection, macrophages increased after 2-3 weeks. Although both populations accumulated in lungs during the infection, DCs decreased in the late stages. Infection induced differential expression of co-stimulatory molecules in these lung APCs, decreasing to basal levels in both APCs in the late stages. A remarkable segregation was found regarding bacillary burden. Many macrophages contained numerous bacilli, but DC contained scarce mycobacteria or none. Mtb-infection also induced delayed accumulation of DC in draining lymph nodes. This delayed recruitment was not associated with a lack of IL-12p40, which was detected from day 3 post-infection. Although AM and lung DCs behave differently during pulmonary tuberculosis, Mtb apparently manipulates both lung APCs subverting early protective responses resulting in disease progression.