The influence of smoke- or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune mediator responses of human bronchoalveolar lavage cells (BALC) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALC containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL) -10 production. PM loaded BALC retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guérin (BCG) and Mycobacterium tuberculosis (M.tb) ΔleuDΔpanCD at equal efficacy as clear non-PM loaded BALC. However, immune responsiveness, such as the production of IL-6 (p=0.015) and tumor necrosis factor (TNF)-α (p= 0.0172) immediately post M.bovis BCG infection, were dramatically lower in black BALC loaded with PM versus clear non-PM loaded BALC. By 24 hour post infection, differential immune responses to M.bovis BCG between black versus clear BALC waned, and instead, production of IL-6 (p= 0.03) and IL-1α (p= 0.04 ) by black BALC were lower versus clear BALC following M.tb ΔleuDΔpanCD infection. Considering that TNFα and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALC loaded with inhaled PM, display lower levels of anti-mycobacterial mediators, and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established.