Mycobacterium tuberculosis PE25/PPE41 protein complex induces activation and maturation of dendritic cells and drives Th2-biased immune responses

Introduction: It is possible that the difference in virulence and prevalence of different strains of Mycobacterium tuberculosis is related to the diverse immune response they evoke in the host. Outbreak strains have been shown to subvert the innate immune response as a potential host evasion mechanism. However, the immunological outcome of the interactions of different clinical strains with different host cells is still not understood. Methodology: Extremely Drug Resistant (XDR) Beijing, a modern lineage clinical strain and a comparator ancient lineage strain, EAI-5, were selected for the present study. The early induction of proinflammatory cytokines in human peripheral blood monocyte derived macrophages (MDM), monocyte derived dendritic cells (MDDC) and whole blood (WB) infected by selected clinical isolates and laboratory strains H37Rv and BCG were assessed. Results: The two clinical strains exhibited distinct patterns of cytokine induction. The ancient lineage strain induced substantially higher expression of all proinflammatory cytokines like TNF-α, IL-1β, IL-12 and chemokines like MCP-1, IL-8. However, the modern lineage strain exhibited suppressed response for the same. Further, the immune responses to two strains were conserved in infected MDM, MDDC and WB i.e. showing similar patterns of response across multiple human hosts. However, the differential response pattern was not observed when bacterial sonicates were used instead of live mycobacteria. Conclusions: The lineage specific patterns in induction of proinflammatory cytokines and chemokines by different M. tuberculosis strains remain similar in macrophage and dendritic cells isolated from different individuals. The present study also confirms that whole cell sonicates of different lineages of M. tuberculosis fail to induce such lineage specific response.

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Mycobacterium tuberculosis PE27 activates dendritic cells and contributes to Th1-polarized memory immune responses during in vivo infection

Immunobiology ◽

10.1016/j.imbio.2015.11.006 ◽

2016 ◽

Vol 221 (3) ◽

pp. 440-453 ◽

Cited By ~ 10

Author(s):

Woo Sik Kim ◽

Jong-Seok Kim ◽

Seung Bin Cha ◽

So Jeong Kim ◽

Hongmin Kim ◽

...

Keyword(s):

Dendritic Cells ◽

Mycobacterium Tuberculosis ◽

Immune Responses

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Fate of Mycobacterium tuberculosis within Murine Dendritic Cells

Infection and Immunity ◽

10.1128/iai.69.2.800-809.2001 ◽

2001 ◽

Vol 69 (2) ◽

pp. 800-809 ◽

Cited By ~ 145

Author(s):

Kendra A. Bodnar ◽

Natalya V. Serbina ◽

JoAnne L. Flynn

Keyword(s):

Nitric Oxide ◽

Bone Marrow ◽

Immune Response ◽

Dendritic Cells ◽

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Intracellular Bacteria ◽

Murine Bone Marrow ◽

Oxide Synthase

ABSTRACT The interaction of microbes with dendritic cells (DCs) is likely to have an enormous impact on the initiation of the immune response against a pathogen. In this study, we compared the interaction ofMycobacterium tuberculosis with murine bone marrow-derived DCs and macrophages (Mφ) in vitro. M. tuberculosis grew equally well within nonactivated DCs and Mφ. Activation of DCs and Mφ with gamma interferon and lipopolysaccharide inhibited the growth of the intracellular bacteria in a nitric oxide synthase-dependent fashion. However, while this activation enabled Mφ to kill the intracellular bacteria, the M. tuberculosis bacilli within activated DCs were not killed. Thus, DCs could restrict the growth of the intracellular mycobacteria but were less efficient than Mφ at eliminating the infection. These results may have implications for priming immune responses to M. tuberculosis. In addition, they suggest that DCs may serve as a reservoir for M. tuberculosis in tissues, including the lymph nodes and lungs.

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Characterisation of secretome-based immune responses of human leukocytes infected with various Mycobacterium tuberculosis lineages

PeerJ ◽

10.7717/peerj.11565 ◽

2021 ◽

Vol 9 ◽

pp. e11565

Author(s):

Benjawan Kaewseekhao ◽

Sittiruk Roytrakul ◽

Yodying Yingchutrakul ◽

Marut Laohaviroj ◽

Kanin Salao ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Mycobacterium Tuberculosis ◽

B Cells ◽

Immune Responses ◽

Antigen Processing ◽

Immune Cell ◽

Cell Types ◽

Label Free ◽

Related Proteins

Background Differences in immune responses against different lineages of Mycobacterium tuberculosis (Mtb), and by different types of immune cell, are still poorly understood. We aimed to compare the secretome-based immune responses among three Mtb lineages and among immune-cell types. The immune responses were also investigated during infection and when the bacilli had been eliminated from the immune cells. Methods Human primary leukocytes were infected with strains representing three lineages of Mtb (East-Asian, Indo-Oceanic and Euro-American). Label-free GeLC MS/MS proteomic analysis of secretomes was performed. The response of each immune-cell type was compared with the appropriate interactome database for each. Results The expression pattern of proteins secreted by Mtb-infected leukocytes differed among Mtb lineages. The ancestral lineage (IO lineage) had a greater ability to activate MMP14 (associated with leukocyte migration) than did the more recent lineages (EA and EuA). During infection, proteins secreted by macrophages, dendritic cells, neutrophils and B-cells were associated with cell proliferation. Following clearance of Mtb, proteins associated with interferon signaling were found in macrophages, dendritic cells and neutrophils: proteins associated with antigen processing were found in B-cells and regulatory T-cells. Expression of immune response-related proteins from many immune-cell types might be suppressed by Mtb infection. Our study has provided a better insight into the host-pathogen interaction and immune response against different Mtb lineages.

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