Effects of picolinic acid on the antimicrobial functions of host macrophages against Mycobacterium avium complex

Picolinic acid (PA) potentiates macrophage (MΦ) antimicrobial activity against intracellular Mycobacterium avium complex (MAC). Here, we studied the mechanisms of this phenomenon using human THP-1 MΦs. First, when PA-treated MAC-infected MΦs were cultured in the presence or absence of reactive oxygen intermediate (ROI) scavengers, nitric oxide synthase (NOS) inhibitors or phospholipase A2 (PLA2) inhibitors, none of these agents blocked the activity of PA in potentiating MΦ anti-MAC activity. Second, when PA was added to the in vitro anti-MAC bactericidal system consisting of either ROIs, reactive nitrogen intermediates (RNIs) or free fatty acid (FFA) molecules, which are the major MΦ antimicrobial effectors, PA inhibited the activity of ROIs and conversely potentiated the activity of RNIs; PA did not affect the activity of FFAs. Third, PA reduced mRNA expression of NADPH oxidase and β-defensin-1 by MAC-infected MΦs, whilst neither cytosolic PLA2 nor CAP37 mRNA expression was affected. Notably, inducible NOS and secretory PLA2 mRNA expression was not detected for MAC-infected MΦs even when given PA treatment. These findings suggest that ROIs, RNIs, FFAs and β-defensin-1 do not play important roles in the PA-induced potentiation of MΦ anti-MAC activity.