Divergent Functions of TLR2 on Hematopoietic and Nonhematopoietic Cells during Chronic <i>Mycobacterium tuberculosis</i> Infection

Konowich, Jill; Gopalakrishnan, Archana; Dietzold, Jillian; Verma, Sheetal; Bhatt, Kamlesh; Rafi, Wasiulla; Salgame, Padmini

doi:10.4049/jimmunol.1601651

Cited by 9 publications

(10 citation statements)

References 51 publications

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“…As a result, it is not clear at which infectious stages TLR2 functions in defense against Mtb infection; it is undecided whether it functions at the acute infectious stage or chronic infectious stage. Some researchers hypothesize that TLR2 plays a protective role during Mtb chronic infection, while it does not affect Mtb acute infection [ 153 , 155 , 156 ]. In contrast, Tjärnlund et al demonstrated that TLR2 has a function in Mtb acute infection (at 3 weeks post infection), but not in Mtb chronic infection (at 8 weeks post infection) [ 50 ].…”

Section: Tlr2 Function In Immune Responses To Mycobacterial Infectionmentioning

confidence: 99%

“…However, the underlying mechanisms behind the TLR2-regulated processes are still not clear and need to be further studied. Except for macrophages, the activation of other hematopoietic and non-hematopoietic cells via TLR2 is also required for host resistance to mycobacterial infection [ 154 , 156 ]. By using various chimeric mice, Konowich et al demonstrated that TLR2 signaling in hematopoietic cells plays a role in controlling bacterial burden and granuloma integrity, while TLR2 signaling in non-hematopoietic cells may play a role in promoting granulomatous inflammation and bacterial dissemination [ 156 ].…”

Section: Tlr2 Function In Mediating the Host–mycobacterial Interactionmentioning

confidence: 99%

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The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

Spaink

2022

Biology

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Innate immunity is considered the first line of defense against microbial invasion, and its dysregulation can increase the susceptibility of hosts to infections by invading pathogens. Host cells rely on pattern recognition receptors (PRRs) to recognize invading pathogens and initiate protective innate immune responses. Toll-like receptor 2 (TLR2) is believed to be among the most important Toll-like receptors for defense against mycobacterial infection. TLR2 has been reported to have very broad functions in infectious diseases and also in other diseases, such as chronic and acute inflammatory diseases, cancers, and even metabolic disorders. However, TLR2 has an unclear dual role in both the activation and suppression of innate immune responses. Moreover, in some studies, the function of TLR2 was shown to be controversial, and therefore its role in several diseases is still inconclusive. Therefore, although TLR2 has been shown to have an important function in innate immunity, its usefulness as a therapeutic target in clinical application is still uncertain. In this literature review, we summarize the knowledge of the functions of TLR2 in host–mycobacterial interactions, discuss controversial results, and suggest possibilities for future research.

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Section: Tlr2 Function In Immune Responses To Mycobacterial Infectionmentioning

confidence: 99%

Section: Tlr2 Function In Mediating the Host–mycobacterial Interactionmentioning

confidence: 99%

The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

Spaink

2022

Biology

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“…The contribution of TLR expression on hematopoietic cells and nonhematopoietic cells during M. tuberculosis infection was evaluated for TLR2 in bone‐marrow chimeric mice. The expression of TLR2 on hematopoietic cells contributes to the control of M. tuberculosis infection, whereas the expression of TLR2 on nonhematopoietic cells may promote the progression of infection 32 . It would be important to investigate the contribution of TLR9 expression on hematopoietic cells and nonhematopoietic cells, given that TLR9 plays a role in the control of M. tuberculosis infection 33 .…”

Section: Airway Epithelial Cells and M Tuberculosis Infectionmentioning

confidence: 99%

Interplay between alveolar epithelial and dendritic cells and Mycobacterium tuberculosis

Rodrigues

Conti

Fraga-Silva

et al. 2020

Journal of Leukocyte Biology

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The innate response plays a crucial role in the protection against tuberculosis development. Moreover, the initial steps that drive the host-pathogen interaction following Mycobacterium tuberculosis infection are critical for the development of adaptive immune response. As alveolar M s, airway epithelial cells, and dendritic cells can sense the presence of M. tuberculosis and are the first infected cells. These cells secrete mediators, which generate inflammatory signals that drive the differentiation and activation of the T lymphocytes necessary to clear the infection. Throughout this review article, we addressed the interaction between epithelial cells and M. tuberculosis, as well as the interaction between dendritic cells and M. tuberculosis. The understanding of the mechanisms that modulate those interactions is critical to have a complete view of the onset of an infection and may be useful for the development of dendritic cell-based vaccine or immunotherapies.

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“…Konowich J. с соавт. [54] выявили, что мыши, дефицитные по TLR2 (TLR2-knockout mice), при хронической туберкулезной инфекции неспособны поддерживать стабильную бактериальную нагрузку, о чем свидетельствует развивающаяся иммунопатология у мышей, проявляющаяся пневмонитом и усиленной клеточной инфильтрацией.…”

Section: Toll-like рецепторыunclassified

Innate immune receptors in development of Mycobacterium tuberculosis infection

Лапштаева

Живечкова

Сычев

et al. 2020

Russian Journal of Infection and Immunity

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According to the World Health Organization, over 10 million new tuberculosis cases are reported annually worldwide. According to the 2017 Federal State Statistics Service Report, incidence rate for active TB infection in the Russian Federation was 109.8 cases per 100,000 population, of which 41.3% accounted for chronic disease form. Regardless of climatic conditions, high prevalence of TB infection, is not only due to high Mycobacterium tuberculosis viability, but also its ability for long persistence in human body and reactivation after an unlimited period of dormancy. The outcome of infection is largely determined by host immunoreactivity and its ability to develop protective immune response. In addition, status of immune system also underlies tuberculosis course after the onset: either as a localized form, or as a form with extensive damage to the lungs and even other organs observed in generalized infection. In recent decades, a great attention was paid to examining mechanisms of adaptive cell immunity played in pathogenesis of TB infection. No doubt, adaptive immunity is a powerful defense system providing a targeted specific immune response, but now it is becoming clear that it represents solely an effector arm of innate immunity. Innate immunity is a phylogenetically more ancient, inherited system largely aimed at ensuring rapid pathogen elimination and preventing development of infection at early stages when adaptive immunity ongoing antigen-specific maturation. Mechanisms of innate immunity mediated by cells, diverse receptors, molecules and their complexes, found on various cells. Activation of innate immunity begins with recognition of conserved molecular groups present in various pathogens called pathogen-associated molecular patterns (PAMPs), which are sensed by pathogen recognition receptors (PRRs). Here, we review current data on the role of innate receptors in recognizing M. tuberculosis-derived PAMPs, production of immunoregulatory cytokines and activation of signaling pathways playing a crucial role in the regulation of necroptosis, apoptosis and autophagy of infected macrophages. Significance of innate mucosal factors in implementing immune response to M. tuberculosis is discussed. In particular, Toll-like receptors, scavenger-receptors, mannose receptor, DC-SIGN etc. were described to participate in development of M. tuberculosis immunity. The data on single nucleotide polymorphic variants for innate genes are shown, which predispose to developing tuberculosis and affecting its course.

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Divergent Functions of TLR2 on Hematopoietic and Nonhematopoietic Cells during Chronic Mycobacterium tuberculosis Infection

Cited by 9 publications

References 51 publications

The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

Interplay between alveolar epithelial and dendritic cells and Mycobacterium tuberculosis

Innate immune receptors in development of Mycobacterium tuberculosis infection

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