Mononuclear phagocyte accumulates a stearic acid derivative during differentiation into macrophages. Effects of stearic acid on macrophage differentiation and Mycobacterium tuberculosis control.

The fatty acid composition of monocytes changes substantially during differentiation into macrophages, increasing the proportion of saturated fatty acids. These changes prompted us to investigate whether fatty acid accumulation in the extracellular milieu could affect the differentiation of bystander mononuclear phagocytes. An esterified fatty acid derivative, stearate, was the only fatty acid that significantly increased in macrophage supernatants, and there were higher levels when cells differentiated in the presence of Mycobacterium tuberculosis H37Rv or purified protein derivative (PPD). Exogenous stearic acid enhanced the expression of HLA-DR and CD64; there was also accumulation of IL-12, TNF-α, IL-6, MIP-1 α and ß and a reduction in MCP-1 and the bacterial load. These results suggested that during differentiation, a derivative of stearic acid, which promotes the process as well as the effector mechanisms of phagocytes against the mycobacterium, accumulates in the cell supernatants.

A Mycobacterium tuberculosis fingerprint in human breath allows tuberculosis detection.

An estimated one-third of tuberculosis (TB) cases go undiagnosed or unreported. Sputum samples, widely used for TB diagnosis, are inefficient at detecting infection in children and paucibacillary patients. Indeed, developing point-of-care biomarker-based diagnostics that are not sputum-based is a major priority for the WHO. Here, in a proof-of-concept study, we tested whether pulmonary TB can be detected by analyzing patient exhaled breath condensate (EBC) samples. We find that the presence of Mycobacterium tuberculosis (Mtb)-specific lipids, lipoarabinomannan lipoglycan, and proteins in EBCs can efficiently differentiate baseline TB patients from controls. We used EBCs to track the longitudinal effects of antibiotic treatment in pediatric TB patients. In addition, Mtb lipoarabinomannan and lipids were structurally distinct in EBCs compared to ex vivo cultured bacteria, revealing specific metabolic and biochemical states of Mtb in the human lung. This provides essential information for the rational development or improvement of diagnostic antibodies, vaccines and therapeutic drugs. Our data collectively indicate that EBC analysis can potentially facilitate clinical diagnosis of TB across patient populations and monitor treatment efficacy. This affordable, rapid and non-invasive approach seems superior to sputum assays and has the potential to be implemented at point-of-care.

Fatty acid profile during the differentiation and infection with Mycobacterium tuberculosis of mononuclear phagocytes of patients with TB and healthy individuals.

The blockade of sPLA-2, as well as the removal of calcium during the infection with Mycobacterium tuberculosis, prevents necrosis in mononuclear phagocytes. In addition, previous evidence indicates that the necrosis is modulated by cytokines and may condition the inflammatory environment. The production of cytokines and chemokines in response to infection with M. tuberculosis, fatty acid profile and the lactate dehydrogenase activity in mononuclear phagocytes from tuberculosis patients and healthy controls were interrelated using a principal component analysis in order to establish whether there was an association between the induction and effector stages of necrosis with the production of cytokines and chemokines. Differentiation increased the ratio of saturated/unsaturated fatty acids. The oleate and palmitate correlated with differentiation, laureate, arachidonate and linolenate with infection and necrosis correlates with the production of IL-10. Monocytes from tuberculosis patients seem to be lees differentiated ex vivo.

Fatty acid derivative, chemokine, and cytokine profiles in exhaled breath condensates can differentiate adult and children paucibacillary tuberculosis patients.

The anti-mycobacterial immune response in adults and children with tuberculosis (TB), as well as the response in bacteriologically positive and negative patients, is different. However, knowledge of the immunological events occurring in the lungs in these clinical situations remains scarce. Exhaled breath condensate (EBC) samples may be useful for studying the inflammatory environment of the lower airways in TB patients. The fatty acid, cytokine, and chemokine profiles in EBC from healthy adults; smear-positive and smear-negative adult patients; and healthy, asthmatic, and TB children were determined using gas chromatography and LUMINEX, respectively. Unsaturated fatty acids, particularly oleate, were increased in TB adults and children compared with healthy individuals. Elevated levels of IL-17 were characteristic of paucibacillary patients (adults and children), whereas elevated MCP-1 (monocyte chemotactic protein-1) levels were characteristic of adult patients (smear-positive and smear-negative). The levels of all of the molecules were comparable to the controls after anti-TB treatment, suggesting that changes in the levels of the molecules detected in the EBC samples were the result of the active pulmonary TB. EBC samples may be an important tool for the detection of potential early biomarkers in the different clinical manifestations of pulmonary TB and a useful tool for the diagnosis of TB, particularly in children.