Interferon-Gamma Improves Macrophages Function against M. tuberculosis in Multidrug-Resistant Tuberculosis Patients

Abstract

Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patient's MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients.

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…153 IFN-γ is important to protective anti-TB immunity and administration has nominal benefit in drug-sensitive, 154 and drug-resistant TB. 155 Although several HDTs show promise in pre-clinical studies, insufficient information is …”

Oral Pathogen Porphyromonas gingivalis Can Escape Phagocytosis of Mammalian Macrophages

“…RAW 264.7 cells behave similarly to classically activated M1 macrophages when exposed to Gram-negative bacteria and LPS [ 81 ]. Both RAW 264.7 and M1 macrophages secrete pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α in response to LPS, unlike M2 macrophages that secrete anti-inflammatory cytokines such as IL-10 and TGF-β, or inactivated M0 macrophages [ 12 , 14 , 81 , 82 , 83 , 84 ]. Additionally, both RAW 264.7 and THP-1 M1 exhibit a similar elongated morphology in culture, while the M0s appear circular ( Figure 3 ).…”

“…However, at 24 h p.i., the appearance of the M0 cells exposed to Gram-negative E. coli and P. gingivalis indicates a change in morphology closer to that of M1s ( Figure 3 ). This could be due to the introduction of LPS, its subsequent binding to TLR4, and the resultant signaling cascade that induces the release of cytokines such as IFN-γ [ 12 , 82 , 83 , 84 ]. The combination of IFN-γ and LPS are typical in classical activation of M1 macrophages ( Figure 1 ) and could be, at least in part, the reason why the M0 change in morphology occurred [ 12 , 14 , 82 , 83 ].…”

Immune Response toward Mycobacterium Tuberculosis Infection

“…During this period, the MTb bacteria can mutate to change its surface receptors and continuously trigger the production of cytokines such as IFN-ϒ. 16,23,24 After the continuous production of cytokines, T cells limit the mobility of macrophages and activate their function. 23 At this stage, "granuloma immune" is formed which in histopathological features is composed of macrophages, neutrophils, monocytes, dendritic cells, and T cells.…”