The histopathological analysis of cellular elements, accessory molecules and cytokines in mycobacterial granulomas from HIV positive and negative individuals

Abstract

The immune response to infection with Mycobacterium tuberculosis (Mtb) involves complex interactions between macrophages, T-cells, cytokines and accessory molecules. Mycobacteria evade the host’s immune response by interfering with cell mediated immune systems. Granulomas are central to the host’s defenses against Mtb. These responses may be modified by immune alterations especially in patients co-infected with Human Immunodeficiency Virus (HIV). This study investigated the immunohistochemical profile of CD4+, CD8+, CD68+, Th-17 (also known as Interleukin-17 cells) and Forkhead box (FOXP3) cells, accessory molecule expression (HLA Class I and II) and selected cytokines (Interleukin 2, 4, 6 and Interferon-) of various cell types within mycobacterial granulomas, in lymph nodes from ten HIV negative and ten HIV positive patients. Tissue from a foreign body granuloma in skin was utilised for comparison. This study illustrated retention of CD4+ lymphocyte numbers within granulomas from HIV negative (-) patients but documented a reversal in the ratio of CD4+ to CD8+cells in granulomas from HIV positive (+) patients. Similar IL-17 cell counts were noted in mycobacterial granulomas from both HIV (-) and HIV (+) patients. CD68 was identified in all macrophages and HLA Class II stained 100% of cells. Mycobacterial granulomas from HIV (-) patients showed marginally lower numbers of HLA Class I cells when compared to those from HIV (+) patients. The percentage of FOXP3 positive cells differed significantly between mycobacterial granulomas from HIV (-) and HIV (+) patients. This study highlights the complex interplay between different cell types and cytokines secreted into the microenvironment that ultimately results in containment of the organism or disease progression. Tuberculosis mono-infection causes variation in the expression of cell markers such as FOXP3 with accompanying noteworthy changes in cytokine production in areas of granuloma formation. The alterations noted in TB and HIV co-infection are even greater and point toward evolution of micro-organism synergism with host demise.