PMID- 33720848 OWN - NLM STAT- MEDLINE DCOM- 20220216 LR - 20230302 IS - 1476-1645 (Electronic) IS - 0002-9637 (Print) IS - 0002-9637 (Linking) VI - 104 IP - 5 DP - 2021 Mar 15 TI - The Pathology of Lymphocytes, Histiocytes, and Immune Mechanisms in Mycobacterium tuberculosis Granulomas. PG - 1796-1802 LID - 10.4269/ajtmh.20-1372 [doi] AB - Granuloma formation is the pathologic hallmark of tuberculosis (TB). Few studies have detailed the exact production of cytokines in human granulomatous inflammation and little is known about accessory molecule expressions in tuberculous granulomas. We aimed to identify some of the components of the immune response in granulomas in HIV-positive and -negative lymph nodes. We investigated the immunohistochemical profiles of CD4+, CD8+, CD68+, Th-17, Forkhead box P3 (FOXP3) cells, accessory molecule expression (human leukocyte antigen [HLA] classes I and II), and selected cytokines (interleukins 2, 4, and 6 and interferon-gamma) of various cells, in granulomas within lymph nodes from 10 HIV-negative (-) and 10 HIV-positive (+) cases. CD4+ lymphocyte numbers were retained in HIV- granulomas, whereas CD4+:CD8 + cell were reversed in HIV+ TB granulomas. CD68 stained all histiocytes. Granulomas from the HIV+ group demonstrated a significant increase in FOXP3 cells. Interleukin-2 cytoplasmic expression was similar in both groups. Interferon-gamma (IFN-gamma) expression was moderately increased, IL-6 was statistically increased and IL-4 expression was marginally lower in cells from HIV- than HIV+ TB granulomas. Greater numbers of cells expressed IFN-gamma and IL-6 than IL-2 and IL-4 in HIV- TB granulomas. This study highlights the varied cytokine production in HIV-positive and -negative TB granulomas and indicates the need to identify localized tissue factors that play a role in mounting an adequate immune response required to halt infection. Although TB mono-infection causes variation in cell marker expression and cytokines in granulomas, alterations in TB and HIV coinfection are greater, pointing toward evolution of microorganism synergism. FAU - Wadee, Reubina AU - Wadee R AD - 1Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, and National Health Laboratory Service (NHLS), Johannesburg, South Africa. FAU - Wadee, Ahmed A AU - Wadee AA AD - 2South African Technology Network, Durban, South Africa. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210315 PL - United States TA - Am J Trop Med Hyg JT - The American journal of tropical medicine and hygiene JID - 0370507 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD68 antigen, human) RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (IL4 protein, human) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-2) RN - 0 (Interleukin-6) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antigens, CD/genetics/immunology MH - Antigens, Differentiation, Myelomonocytic/genetics/immunology MH - CD4-Positive T-Lymphocytes/*immunology/microbiology/virology MH - CD8-Positive T-Lymphocytes/*immunology/microbiology/virology MH - Coinfection MH - Forkhead Transcription Factors/genetics/immunology MH - Gene Expression MH - Granuloma/*immunology/microbiology/pathology/virology MH - HIV/immunology/pathogenicity MH - HIV Infections/*immunology/microbiology/pathology/virology MH - Histiocytes/*immunology/microbiology/virology MH - Humans MH - Immunohistochemistry MH - Interferon-gamma/genetics/immunology MH - Interleukin-2/genetics/immunology MH - Interleukin-4/genetics/immunology MH - Interleukin-6/genetics/immunology MH - Latent Tuberculosis/*immunology/microbiology/pathology/virology MH - Lymph Nodes/immunology/microbiology/virology MH - Lymphocyte Count MH - Mycobacterium tuberculosis/immunology/pathogenicity MH - Th17 Cells/*immunology/microbiology/virology MH - Tuberculosis, Lymph Node/*immunology/microbiology/pathology/virology PMC - PMC8103466 COIS- Disclosure: The experimental work of this manuscript has been submitted and awarded by the University of the Witwatersrand for the degree of Master of Medicine, to R. Wadee. EDAT- 2021/03/16 06:00 MHDA- 2022/02/17 06:00 PMCR- 2022/05/01 CRDT- 2021/03/15 17:21 PHST- 2020/10/20 00:00 [received] PHST- 2021/01/24 00:00 [accepted] PHST- 2021/03/16 06:00 [pubmed] PHST- 2022/02/17 06:00 [medline] PHST- 2021/03/15 17:21 [entrez] PHST- 2022/05/01 00:00 [pmc-release] AID - tpmd201372 [pii] AID - 10.4269/ajtmh.20-1372 [doi] PST - epublish SO - Am J Trop Med Hyg. 2021 Mar 15;104(5):1796-1802. doi: 10.4269/ajtmh.20-1372.