Circulating Monocyte-Like Myeloid Derived Suppressor Cells and CD16 Positive Monocytes Correlate With Immunological Responsiveness of Tuberculosis Patients

Abstract

Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of Mycobacterium tuberculosis (Mtb-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after Mtb-Ag stimulation in HR-TB. We also found that LR-TB displayed the highest percentages of circulating M-MDSC. These results demonstrate that CD16 positive monocytes and M-MDSC frequencies could be used as another immunological classification parameter. Interestingly, in LR-TB, frequencies of CD16 positive monocytes and M-MDSC were restored after only three weeks of anti-TB treatment. Together, our findings show a link between the immunological status of TB patients and the levels of different circulating myeloid cell populations.

Cytokine upsurge among drug-resistant tuberculosis endorse the signatures of hyper inflammation and disease severity

“…All nucleated cells produce cytokines with either antagonistic or synergistic effects 11 depends on the infection milieu and the host-pathogen interaction. The release of Th1 and Th17 inflammatory cytokines (IL-2, www.nature.com/scientificreports/ TNF-α, IFN-γ, IL-12 and IL-17) are correlated with host protective responses against TB infection 27,28 and that was in connection with MTB clearance and sterilization of granulomas in macaques 17 . The so-called protective cytokines switch to pathological responses due to their overproduction and loss of balance in DR-TB and DS-TB from our study as stated earlier by Kumar et al, 2019 where the type 1 and 17 cytokines assist disease pathology in PTB 8 .…”

Beyond the Clinic: The Activation of Diverse Cellular and Humoral Factors Shapes the Immunological Status of Patients with Active Tuberculosis

“…Cut-off values to differentiate be-tween the two populations of LR TB and HR TB patients were previously established by Pasquinelli et al and Amiano 2022 [26,27]. The fulfilment of two of the three mentioned criteria was required to assign a patient to the corresponding group [26,27]. Besides, it was demonstrated that common clinical parameters analyzed in TB patients paralleled immunological criteria studied in HR and LR individuals [7,26].…”

Advances in the study of myeloid-derived suppressor cells in infectious lung diseases

“…The results of studies on TB patients also confirm the correlation between MDSCs and disease ( Table 2 ). The frequency of both subpopulations of MDSCs was elevated in PBMC of patients with active TB, was dominated by M-MDSCs, reduced the immunological function of lymphocytes in TB patients, and was proportional to the severity of the disease ( 67 – 70 ). Other investigations have shown that the levels of PMN-MDSCs are elevated in the peripheral blood and bronchoalveolar lavage fluid of patients with active TB, and that these levels correlate with plasma nitric oxide levels ( 6 , 72 ).…”