Neutrophils: Innate Effectors of TB Resistance?

Kroon, Elouise E.; Coussens, Anna K.; Kinnear, Craig; Orlova, Marianna; Möller, Marlo; Seeger, Allison; Wilkinson, Robert J.; Hoal, Eileen G.; Schurr, Erwin

doi:10.3389/fimmu.2018.02637

Cited by 58 publications

(55 citation statements)

References 163 publications

(192 reference statements)

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“…In reported cases of M. smegmatis infection, histopathological analysis shows skin ulceration and subcutaneous necrosis, with treatment involving aggressive surgical debridement of the infected tissue [12]. Neutrophils are recognized as initial effectors of acute inflammation during mycobacterial infections [33][34][35][36][37]. For example, neutrophils were recruited as early as 15 min after M. smegmatis subcutaneous inoculation in a BALB/c mouse model [38].…”

Section: Discussionmentioning

confidence: 99%

Human Neutrophil Granule Exocytosis in Response to Mycobacterium smegmatis

et al. 2020

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Mycobacterium smegmatis rarely causes disease in the immunocompetent, but reported cases of soft tissue infection describe abscess formation requiring surgical debridement for resolution. Neutrophils are the first innate immune cells to accumulate at sites of bacterial infection, where reactive oxygen species and proteolytic enzymes are used to kill microbial invaders. As these phagocytic cells play central roles in protection from most bacteria, we assessed human neutrophil phagocytosis and granule exocytosis in response to serum opsonized or non-opsonized M. smegmatis mc2. Although phagocytosis was enhanced by serum opsonization, M. smegmatis did not induce exocytosis of secretory vesicles or azurophilic granules at any time point tested, with or without serum opsonization. At early time points, opsonized M. smegmatis induced significant gelatinase granule exocytosis compared to non-opsonized bacteria. Differences in granule release between opsonized and non-opsonized M. smegmatis decreased in magnitude over the time course examined, with bacteria also evoking specific granule exocytosis by six hours after addition to cultured primary single-donor human neutrophils. Supernatants from neutrophils challenged with opsonized M. smegmatis were able to digest gelatin, suggesting that complement and gelatinase granule exocytosis can contribute to neutrophil-mediated tissue damage seen in these rare soft tissue infections.

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Section: Discussionmentioning

confidence: 99%

Human Neutrophil Granule Exocytosis in Response to Mycobacterium smegmatis

et al. 2020

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“…Neutrophil granulocytes are the most widely present cell population within BAL and sputum in patients with active TB (27). There is evidence of their role as defense mechanisms against Mtb.…”

Section: Innate Immune Response Against Mycobacterium Tuberculosismentioning

confidence: 99%

“…Moreover, as with many immune mechanisms, neutrophils do not only play a positive role, but can eventually constitute a negative element, causing tissue damage through production and subsequent release of their antimicrobial products (27). To this phenomenon, it must be added the potentially negative interaction with lymphocytes.…”

Section: Innate Immune Response Against Mycobacterium Tuberculosismentioning

confidence: 99%

Immune Response to Mycobacterium tuberculosis: A Narrative Review

et al. 2019

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The encounter between Mycobacterium tuberculosis (Mtb) and the host leads to a complex and multifaceted immune response possibly resulting in latent infection, tubercular disease or to the complete clearance of the pathogen. Macrophages and CD4 + T lymphocytes, together with granuloma formation, are traditionally considered the pillars of immune defense against Mtb and their role stands out clearly. However, there is no component of the immune system that does not take part in the response to this pathogen. On the other side, Mtb displays a complex artillery of immune-escaping mechanisms capable of responding in an equally varied manner. In addition, the role of each cellular line has become discussed and uncertain further than ever before. Each defense mechanism is based on a subtle balance that, if altered, can lean to one side to favor Mtb proliferation, resulting in disease progression and on the other to the host tissue damage by the immune system itself. Through a brief and complete overview of the role of each cell type involved in the Mtb response, we aimed to highlight the main literature reviews and the most relevant studies in order to facilitate the approach to such a complex and changeable topic. In conclusion, this narrative mini-review summarizes the various immunologic mechanisms which modulate the individual ability to fight Mtb infection taking in account the major host and pathogen determinants in the susceptibility to tuberculosis.

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“…Multiple receptors including TLRs, C-type lectin receptors (CLRs), and cytokine receptors have been implicated in the interaction between neutrophils, M. tuberculosis, and proinflammatory cytokines [57]. Moreover, neutrophils have a great implication in the acute inflammatory response to M. tuberculosis [58]. The impact of hyperglycemia on neutrophils in TB has been investigated that increased adhesion and integrin expression, reduced chemotaxis, defected phagocytes, and reduced microbicidal activity as compared with neutrophils from euglycemic controls [43] (Figure 1).…”

Section: Effects and Immunological Mechanism Of Diabetes On Tubercmentioning

confidence: 99%

Immunological Impacts of Diabetes on the Susceptibility of Mycobacterium tuberculosis

Ayelign

Negash

Genetu

et al. 2019

Journal of Immunology Research

123

103

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The interaction between diabetes and major world infections like TB is a major public health concern because of rapidly rising levels of diabetes. The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a major global public health problem. Diabetes mellitus is a major risk factor for the development of active and latent tuberculosis. Immune mechanisms contributing to the increased susceptibility of diabetic patients to TB are due to the defects in bacterial recognition, phagocytic activity, and cellular activation which results in impaired production of chemokines and cytokines. The initiation of adaptive immunity is delayed by impaired antigen-presenting cell (APC) recruitment and function in hyperglycemic host, which results in reduced frequencies of Th1, Th2, and Th17 cells and its secretion of cytokines having a great role in activation of macrophage and inflammatory response of tuberculosis. In addition, impaired immune response and killing of intracellular bacteria potentially increase bacterial load, chronic inflammation, and central necrosis that facilitate bacterial dissemination and miliary tuberculosis. Understanding of the immunological and biochemical basis of TB susceptibility in diabetic patients will tell us the rational development of implementation and therapeutic strategies to alleviate the dual burden of the diseases. Therefore, the aim of this review was focused on the association between diabetes and tuberculosis, focusing on epidemiology, pathogenesis, and immune dysfunction in diabetes mellitus, and its association with susceptibility, severity, and treatment outcome failure to tuberculosis.

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Neutrophils: Innate Effectors of TB Resistance?

Cited by 58 publications

References 163 publications

Human Neutrophil Granule Exocytosis in Response to Mycobacterium smegmatis

Human Neutrophil Granule Exocytosis in Response to Mycobacterium smegmatis

Immune Response to Mycobacterium tuberculosis: A Narrative Review

Immunological Impacts of Diabetes on the Susceptibility of Mycobacterium tuberculosis

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