Differential Responses by Human Macrophages to Infection With Mycobacterium tuberculosis and Non-tuberculous Mycobacteria

Abstract

Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) are formidable causes of lung diseases throughout the world. While MTB is considered to be more virulent than NTM, host factors also play a key role in disease development.To elucidate whether there are differential immune responses to various mycobacteria, THP-1 macrophages were temporally infected with MTB H37Rv or with four different NTM species. We found that cells infected with MTB had greater bacterial burden and p65 nuclear factor-kappa B (NF-κB) activation than cells infected with NTM. There was also differential expression of mRNA for interleukin-1-β (IL-1β), IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) with no distinct pattern of mRNA expression among the different mycobacteria. In contrast, at the protein level, some generalizations can be made of the cytokines and chemokines expressed. Compared to uninfected cells, the rapid-growing Mycobacterium smegmatis but not Mycobacterium abscessus induced significantly greater pro-inflammatory cytokines and IL-10, whereas both NTM individually induced greater levels of chemokines. Compared to uninfected control cells, the two slow-growing NTM and MTB differentially induced cytokine expression with Mycobacterium avium inducing more pro-inflammatory cytokines and IL-10, whereas M. avium, Mycobacterium intracellulare, and MTB inducing greater but similar levels of chemokines. MTB-infected THP-1 cells also demonstrated lower level of phagosomelysosome fusion and apoptosis than NTM-infected cells while there were differences in these macrophage functions among the NTM species. Interestingly, M. intracellulare, M. avium, and MTB have similar levels of autophagosome formation, but the levels displayed by all three were lower than for M. smegmatis and M. abscessus. This study demonstrates the differences in bacterial burden and macrophage effector functions among several clinically relevant mycobacterial species. Such disparities may, in part, account for differences in clinical outcomes among patients infected with various species of NTM as has been seen for different strains of MTB.

Mycobacterial PPE13 activates inflammasome by interacting with the NATCH and LRR domains of NLRP3

“…Previous studies indicated that M. smegmatis strain induces IL-1β secretion. [34][35][36] Our results showed that the recombinant M. smegmatis strain expressing PPE13 (named as Ms_PPE13) enhanced cell death and IL-1β secretion in J774A.1, BMDMs, and THP-1 cells. PPE13 induces the transcription of pro-IL-β, raising the possibility that increased IL-1β protein may be due to increased transcription.…”

A bioinformatics analysis to identify novel biomarkers for prognosis of pulmonary tuberculosis

“…Studies believed that patients have various physiological and biochemical responses to NTM infections and MTB. Feng et al [ 33 ] made a study on macrophages and believed that the activation of NF-κB in MTB patients was more significant in comparison with that in patients with NTM infections, and there were differences in IL-8, IL-10 and TNF-α in different infections. Additionally, Nurlela et al [ 34 ] also discovered that level of TNF-α in pleural fluid of patients with NTM infections and MTB was different, with that in MTB sufferers significantly higher.…”

Tuberculosis diagnostics: overcoming ancient challenges with modern solutions

“…The culturing of Mtb raises several issues, mainly relating to the growth rate of Mtb, which is substantially slower than other pathogenic organisms, most probably due to a selective pressure at which faster growing Mycobacterium spp. induces a greater immune response [27]. It can often take more than four weeks for Mtb to produce colonies using traditional Lowenstein-Jensen medium (LJ) [28].…”