PMID- 35763913 OWN - NLM STAT- MEDLINE DCOM- 20220810 LR - 20220829 IS - 1873-281X (Electronic) IS - 1472-9792 (Linking) VI - 135 DP - 2022 Jul TI - Stimulated expression of ELR+ chemokines, VEGFA and TNF-AIP3 promote mycobacterial dissemination in extrapulmonary tuberculosis patients and Cavia porcellus model of tuberculosis. PG - 102224 LID - S1472-9792(22)00061-0 [pii] LID - 10.1016/j.tube.2022.102224 [doi] AB - Pathogenic mycobacteria induce and accelerate blood vessel formation driven by extensive inflammation during granuloma formation, which is a central feature of mycobacterial pathogenesis. Tumor necrosis factor-alpha (TNF-alpha) enhances the expression of vascular endothelial growth factor (VEGF) and glutamic acid-leucine-arginine (ELR+) chemokines, which are potent inducers of vascularization. Most of the reported research work contends that VEGF growth factor induces neovascularization in human tuberculosis (TB) patients, but the evidence is inconclusive. Considerable ambiguity exists concerning the factors responsible for miliary tuberculosis. To identify such factors, we proposed an alternative explanation that could be found in miliary tuberculosis (MTB) cases. We performed a comparative analysis of angiogenic factors TNF-alpha, VEGF, and angiogenic ELR+ CXC and CC chemokine ligands in extrapulmonary tuberculosis (EPTB) and pulmonary tuberculosis (PTB) patients. To observe the relationship of these factors with the severity of bacterial burden, guinea pigs were infected with Mycobacterium tuberculosis (M.tb) and levels of the angiogenic factors were examined at different time intervals. Expression of these factors also exhibited a significant positive correlation with bacterial burden in other organs like the spleen, liver, and lymph nodes. We demonstrated statistical data on bacterial burden at different time points following the dissemination of infection in guinea pigs. In this study, we observed that there was a stimulated increase in the expression of ELR+ chemokines and VEGF in EPTB patients as compared to PTB patients. Following increased dissemination, the host immune response clears bacteria from the lungs during disease progression in guinea pigs. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Davuluri, Kusuma Sai AU - Davuluri KS AD - Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282001, India. Electronic address: 604dks@gmail.com. FAU - Singh, Amit Kumar AU - Singh AK AD - Department of Animal Experimentation and Facility, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 281406, India. Electronic address: dramit.icmr@gmail.com. FAU - Kumar, Vimal AU - Kumar V AD - Department of Animal Experimentation and Facility, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 281406, India. Electronic address: drvkyadava@gmail.com. FAU - Singh, Shoor Vir AU - Singh SV AD - Department of Biotechnology, GLA University, Mathura, 281406, India. Electronic address: shoorvir_singh@rediffmail.com. FAU - Singh, Ajay Vir AU - Singh AV AD - Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282001, India. Electronic address: avsjalma@gmail.com. FAU - Kumar, Santhosh AU - Kumar S AD - Department of Pulmonary Medicine, SNMC, Agra, 282001, India. FAU - Yadav, Rajbala AU - Yadav R AD - Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282001, India. FAU - Kushwaha, Shweta AU - Kushwaha S AD - Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282001, India. FAU - Chauhan, Devendra Singh AU - Chauhan DS AD - Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282001, India. Electronic address: devchauhan01@yahoo.co.in. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220622 PL - Scotland TA - Tuberculosis (Edinb) JT - Tuberculosis (Edinburgh, Scotland) JID - 100971555 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 2.7.4.8 (Guanylate Kinases) RN - EC 2.7.4.8 (MAGI1 protein, human) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Cell Adhesion Molecules MH - Chemokines MH - Guanylate Kinases MH - Guinea Pigs MH - Humans MH - *Mycobacterium tuberculosis MH - *Tuberculosis, Miliary MH - *Tuberculosis, Pulmonary MH - Tumor Necrosis Factor-alpha MH - Vascular Endothelial Growth Factor A OTO - NOTNLM OT - Dissemination OT - ELR+ chemokines OT - Mycobacterium tuberculosis OT - Pro-inflammatory cytokine OT - T-cell mediated immunity EDAT- 2022/06/29 06:00 MHDA- 2022/08/11 06:00 CRDT- 2022/06/28 18:16 PHST- 2022/02/04 00:00 [received] PHST- 2022/06/06 00:00 [revised] PHST- 2022/06/12 00:00 [accepted] PHST- 2022/06/29 06:00 [pubmed] PHST- 2022/08/11 06:00 [medline] PHST- 2022/06/28 18:16 [entrez] AID - S1472-9792(22)00061-0 [pii] AID - 10.1016/j.tube.2022.102224 [doi] PST - ppublish SO - Tuberculosis (Edinb). 2022 Jul;135:102224. doi: 10.1016/j.tube.2022.102224. Epub 2022 Jun 22.