CD11b⁺ Dendritic Cell-Mediated Anti-Mycobacterium tuberculosis Th1 Activation Is Counterregulated by CD103⁺ Dendritic...

Mycobacterium tuberculosis, the pathogen causing pulmonary tuberculosis (TB) in humans, has evolved to delay Th1 immunity in the lung. Although conventional dendritic cells (cDCs) are known to be critical to the initiation of T cell immunity, the differential roles and molecular mechanisms of migratory CD11b⁺ and CD103⁺ cDC subsets in anti-M. tuberculosis Th1 activation remain unclear. Using a murine model of pulmonary M. tuberculosis infection, we found that slow arrival of M. tuberculosis-bearing migratory CD11b⁺ and CD103⁺ cDCs at the draining lymph nodes preceded the much-delayed Th1 immunity and protection in the lung. Contrary to their previously described general roles in Th polarization, CD11b⁺ cDCs, but not CD103⁺ cDCs, were critically required for Th1 activation in draining lymph nodes following M. tuberculosis infection. CD103⁺ cDCs counterregulated CD11b⁺ cDC-mediated Th1 activation directly by producing the immune-suppressive cytokine IL-10. Thus, our study provides new mechanistic insights into differential Th immune regulation by migratory cDC subsets and helps to develop novel vaccines and therapies.