Abstract
A granuloma, a pathologic hallmark of tuberculosis (TB), is a complex cellular structure that develops at the site of Mycobacterium tuberculosis (Mtb) infection and is comprised of different immune cell types. Severe pulmonary TB in humans is characterized by the presence of heterogeneous granulomas, ranging from highly cellular to solid/non-necrotic and necrotic lesions, within the lungs. The host-Mtb interactions within the granulomas dictate the containment of Mtb infection or its progression into a necrotic, cavitary disease. However, the immune environment in various granulomas is poorly understood. The myeloid-derived suppressor cells (MDSCs) are key immune cells that regulate the protective versus permissive host responses against Mtb infection. However, their contexture within the lung granulomas remains unclear. In this study, using single and multiplex immunohistochemical staining, we analyzed the distribution of MDSCs, macrophages, CD4+ T cells and their immunometabolic and effector function states in the solid/non-necrotic and necrotic granulomas in patients with active pulmonary TB. We found increased MDSCs with elevated expression of immunosuppressive molecules in the solid/non-necrotic granulomas. In contrast, cells in the solid and necrotic granulomas produced similar levels of IL-6 and IL-10. Our findings suggest that MDSCs are present in solid/non-necrotic granuloma, which may play an essential role in the progression into a necrotic lesion, thus exacerbating disease pathology and transmission.
Highlights
Tuberculosis (TB) has been a leading cause of mortality and morbidity around the globe for decades
In this study, we applied immunohistostaining with combinations of antibodies and a sequential probing/reprobing method on lung sections from TB patients to analyze the distribution and the functional state of myeloid-derived suppressor cells (MDSCs) in solid/non-necrotic granulomas compared with necrotic granulomas
Heterogeneous granuloma types exist in the lungs of TB patients, and the maturation of each granuloma occurs as a continuous process and is distinctly regulated within the infected host
Summary
Tuberculosis (TB) has been a leading cause of mortality and morbidity around the globe for decades. Following inhalation into the lungs, Mtb interacts with phagocytes, which elicit an immune response to recruit more leukocytes to the site of infection to eliminate the pathogen [2]. The recruitment and retention of immune cells, including monocytes, dendritic cells, granulocytes, and lymphocytes from the blood to the site of infection, leads to the formation of granuloma, a hallmark in TB pathology [3,4,5]. Solid/non-necrotic granulomas contain “caseum,” a cheese-like material derived from the necrosis of Mtbinfected macrophages and monocytes. This acellular region is surrounded by epithelioid macrophages and a lymphocytic cuff consisting of B and T lymphocytes. During the progression of the disease, some solid/non-necrotic granulomas develop cavitation (necrotic granuloma), which flows into the airways and enables the expulsion of caseum contents in the form of sputum, with abundant Mtb, thereby facilitating bacterial dissemination and the transmission of infection [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
