Abstract
Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Myeloid derived suppressor cells (MDSC) have been shown to be expanded during TB, but their role in human TB pathogenesis is not clear. We evaluated the frequency of circulating MDSC by flow-cytometry in 19 patients with active TB, 18 with latent TB infection (LTBI), and 12 healthy donors (HD) as control. Moreover, we investigated the capacity of MDSC to modulate the mycobactericidal activity of monocytes. The association between MDSC level and TB chest X-ray severity score was analyzed. We observed that, unlike active TB, polymorphonuclear (PMN)-MDSC are not expanded in LTBI patients, and, by performing a receiver operating characteristic (ROC) curve analysis, we found that PMN-MDSC frequency supported the discrimination between active disease and LTBI. Interestingly, we observed an association between PMN-MDSC levels and the severity of TB disease evaluated by chest X-ray. Specifically, PMN-MDSC frequency was higher in those classified with a low/mild severity score compared to those classified with a high severity score. Moreover, PMN-MDSC can impact mycobacterial growth by inducing ROS production in Bacillus Calmette et Guerin (BCG)-infected monocytes. This effect was lost when tested with M. tuberculosis (MTB), In conclusion, our data indicate that the elevated frequency of PMN-MDSC in IGRA-positive individuals is associated with active TB. Our findings also pointed out a beneficial role of PMN-MDSC during human active TB, most likely associated with the limitation of inflammation-induced tissue damage.
Highlights
Tuberculosis (TB) remains a leading cause of global mortality
In the present study we demonstrate that, unlike active TB, polymorphonuclear (PMN)-myeloidderived suppressor cells (MDSC) are not expanded in latent TB infection” (LTBI) patients, and the PMN-MDSC frequency might be used to discriminate between active disease and LTBI
We firstly evaluated the frequency of MDSC in patients with active TB, LTBI and healthy donors (HD)
Summary
Tuberculosis (TB) remains a leading cause of global mortality Pulmonary TB can present with mild, moderate, or severe respiratory and systemic symptoms, with involvement of single or multiple lung lobes The factors defining this variety are unclear and likely involve both microbial and immunologic components. The identification of protective markers of immune response are still lacking, a number of studies have shown that CD8 T cell– mediated killing of infected host cells is crucial for the defense against Mycobacterium tuberculosis (MTB) infection [1, 2]. Regulatory T cells (Tregs) are increased in active TB [4], and limit potentially protective immune responses and facilitate microbial replication during TB as well as in other diseases [5, 6]. A third group of MDSC defined early-stage MDSC (e-MDSC) has been identified as HLA-DR- CD33+ CD15- Lin(CD3- CD56- CD19- CD14-) [9]
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