Immune Response toward Mycobacterium Tuberculosis Infection


Abdi Dzul Ikram Hasanuddin
Nanang Roswita
Ivan Virnanda Amu


Understanding the human immune response toward Mycobacterium tuberculosis infection is important for controlling its infection. Its transmission through the air consists of "droplets nuclei" containing TB bacilli. After initial infection, the human body will provide diverse immune responses and will determine different clinico-histopathologic finding. This response starts from innate immunity that consists of phagocytosis by distal alveolar macrophages or nasal microfold cells, then will be continued by dendritic cells to be transferred to mediastinal lymph nodes to induced adaptive immune responses. This response is mediated by cells through IFN- γ signaling which will enhance phagocytosis. If this response is effective, there will be a latent infection with an initial histopathological finding of caseosa granulomas and predominantly followed by chronic granulomas. In a few cases, it can be reactivated via the IL-10 activation pathway and exogenous factors, it will induce a great adaptive immune reaction and provide more severe clinico-histopathological manifestation. The existence of the human body's immune response to Mycobacterium tuberculosis, etiher innate or adaptive immunity will determine the clinical course and pathology that will occur.



1. Keshavjee, S. & Farmer, P. E. Tuberculosis, Drug Resistance, and the History of Modern Medicine. N. Engl. J. Med. 367, 931–936 (2012).
2. Talbot, E. A. & Raffa, B. J. Mycobacterium tuberculosis. in Molecular Medical Microbiology 1637–1653 (Elsevier, 2015).
3. Tuberculosis (TB).
4. Marlina Indah. Tuberculosis. Infodatin Kementerian Kesehatan RI 1–6 (2018).
5. Fogel, N. Tuberculosis: A disease without boundaries. Tuberculosis 95, 527–531 (2015).
6. Berry, M. P. R., Blankley, S., Graham, C. M., Bloom, C. I. & O’Garra, A. Systems approaches to studying the immune response in tuberculosis. Curr. Opin. Immunol. 25, 579–587 (2013).
7. Thillai, M., Pollock, K., Pareek, M. & Lalvani, A. Interferon-gamma release assays for tuberculosis: current and future applications. Expert Rev. Respir. Med. 8, 67–78 (2014).
8. Pitt, J. M., Blankley, S., McShane, H. & O’Garra, A. Vaccination against tuberculosis: how can we better BCG? Microb. Pathog. 58, 2–16 (2013).
9. Shinnick, T. M. & Good, R. C. Diagnostic mycobacteriology laboratory practices. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 21, 291–299 (1995).
10. Riley, L. W. Of mice, men, and elephants: Mycobacterium tuberculosis cell envelope lipids and pathogenesis. J. Clin. Invest. 116, 1475–1478 (2006).
11. Laboratory detection and identification of mycobacteria: approved guideline. (Clinical and Laboratory Standards Institute, 2008).
12. Cole, S. T. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544 (1998).
13. Valway, S. E. et al. An outbreak involving extensive transmission of a virulent strain of Mycobacterium tuberculosis. N. Engl. J. Med. 338, 633–639 (1998).
14. Manca, C. et al. Mycobacterium tuberculosis CDC1551 Induces a More Vigorous Host Response In Vivo and In Vitro, But Is Not More Virulent Than Other Clinical Isolates. J. Immunol. 162, 6740–6746 (1999).
15. Drain. Tuberculosis, Patophysiology and Transmission. in Tuberculosis Clinical Intensive (2016).
16. De Martino, M., Galli, L. & Chiappini, E. Reflections on the immunology of tuberculosis: will we ever unravel the skein? BMC Infect. Dis. 14 Suppl 1, S1 (2014).
17. Nair, V. R. et al. Microfold Cells Actively Translocate Mycobacterium tuberculosis to Initiate Infection. Cell Rep. 16, 1253–1258 (2016).
18. Hossain, M. M. & Norazmi, M.-N. Pattern recognition receptors and cytokines in Mycobacterium tuberculosis infection--the double-edged sword? BioMed Res. Int. 2013, 179174 (2013).
19. Liu, C. H., Liu, H. & Ge, B. Innate immunity in tuberculosis: host defense vs pathogen evasion. Cell. Mol. Immunol. 14, 963–975 (2017).
20. Rajaram, M. V. S. et al. Mycobacterium tuberculosis activates human macrophage peroxisome proliferator-activated receptor gamma linking mannose receptor recognition to regulation of immune responses. J. Immunol. Baltim. Md 1950 185, 929–942 (2010).
21. Ernst, J. D. The immunological life cycle of tuberculosis. Nat. Rev. Immunol. 12, 581–591 (2012).
22. Cruz-Knight, W. & Blake-Gumbs, L. Tuberculosis: an overview. Prim. Care 40, 743–756 (2013).
23. Shaler, C. R., Horvath, C. N., Jeyanathan, M. & Xing, Z. Within the Enemy’s Camp: contribution of the granuloma to the dissemination, persistence and transmission of Mycobacterium tuberculosis. Front. Immunol. 4, (2013).
24. Khan, T. A. et al. Interferon-Gamma Improves Macrophages Function against M. tuberculosis in Multidrug-Resistant Tuberculosis Patients. Chemother. Res. Pract. 2016, 7295390 (2016).
25. Chao, M. C. & Rubin, E. J. Letting sleeping dos lie: does dormancy play a role in tuberculosis? Annu. Rev. Microbiol. 64, 293–311 (2010).
26. Goldman L & Schafer AI. Tuberculosis: disease overview. in Goldman’s cecil medicine: expert consult premium edition (Saunders Elsevier, 2011).
27. Hunter, R. L. Tuberculosis as a three-act play: A new paradigm for the pathogenesis of pulmonary tuberculosis. Tuberc. Edinb. Scotl. 97, 8–17 (2016).
28. Koch, A., Cox, H. & Mizrahi, V. Drug-resistant tuberculosis: challenges and opportunities for diagnosis and treatment. Curr. Opin. Pharmacol. 42, 7–15 (2018).