Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and IL-10

Lewkowicz, Natalia; Mycko, Marcin P.; Przygodzka, Patrycja; Ćwiklińska, Hanna; Cichalewska, Maria; Matysiak, Mariola; Selmaj, Krzysztof; Lewkowicz, Przemysław

doi:10.1038/mi.2015.66

Cited by 79 publications

(86 citation statements)

References 41 publications

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“…Mounting evidence has been implicated that macrophages especially the M2 subset could induce Tregs and, inversely, Treg cells can also promote macrophage efferocytosis during inflammation resolution in zymosan‐induced peritonitis and LPS‐induced lung injury . Although few studies have demonstrated the direct effect between Treg and neutrophil, it is still reported that Treg can induce il‐10‐producing neutrophils . At present, there is a lack of adequate evidence to explicitly clarify the intricate interaction between various immune cells.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

et al. 2019

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Summary Acute respiratory distress syndrome (ARDS) induces a strong local infiltration of regulatory T‐cells (Tregs) in the lungs. However, at present, there remains a lack of adequate evidence showing the direct effect of Tregs on pulmonary repair and the related mechanisms of ARDS. Therefore, in this project, we studied the impact of Tregs on lipopolysaccharide (LPS)‐induced ARDS and pulmonary inflammation. Surprisingly, we found that depletion of Tregs by injection of PC61 anti‐CD25 antibody not only interfered with the inflammation resolution, such as inhibited total cell infiltration into the alveolar space, downregulated neutrophils, upregulated macrophages, but also impaired pulmonary epithelium and endothelial cell proliferation. Consistent with the attenuation of pulmonary repair, we found that the Th1 and Th17 immune responses were also impaired in Treg‐depleted mice, suggesting that the presence of Tregs is vital for tissue repair, as Tregs modulate and promote the Th immune response in LPS‐induced pulmonary inflammation.

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Section: Discussionmentioning

confidence: 99%

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

et al. 2019

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“…While human neutrophil IL-10 production has been shown by a few groups to be inhibited due to inactivity of the IL-10 gene locus, others have shown human neutrophil IL-10 production in response to fungal pathogens (28) and through direct-cell contact (29). Differences in the findings shown here may be due to the stimuli used to activate human neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

et al. 2017

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In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment that Mycobacterium tuberculosis (M.tb) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter the M.tb surface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on the M.tb cell wall surface and release of M.tb cell wall fragments into the environment. Typically, one of the first host immune cells at the site of M.tb infection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response to M.tb during infection. We hypothesized that exposure of neutrophils to ALF-induced M.tb released cell wall fragments would prime neutrophils to control M.tb infection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control of M.tb growth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-induced M.tb fragments could further contribute to the control of M.tb growth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site.

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“…Consistently, such suppressor neutrophils could be identified at sites of gram-negative bacteria-induced inflammation, such as the periodontal pockets of chronic periodontitis patients, but not at sites of aseptic inflammation (cerebrospinal fluid of patients with neuromyelitis optica) [204]. The notion that neutrophils can transform into IL-10–producing cells is in line with the emerging concept that neutrophils do not represent a homogeneous population but exhibit functional plasticity that allows them to also act as regulatory cells under certain conditions [18,205].…”

Section: Hyper-reactive and Suppressor Neutrophil Populations In Cmentioning

confidence: 97%

“…A recent study has shown that human neutrophils produce IL-10 upon direct contact with LPS-stimulated regulatory T cells (Tregs), mediated by Mac-1 and ICAM-1 on neutrophils and Tregs, respectively [204]. Consistently, such suppressor neutrophils could be identified at sites of gram-negative bacteria-induced inflammation, such as the periodontal pockets of chronic periodontitis patients, but not at sites of aseptic inflammation (cerebrospinal fluid of patients with neuromyelitis optica) [204].…”

Section: Hyper-reactive and Suppressor Neutrophil Populations In Cmentioning

confidence: 99%

“…The authors of this study, nevertheless, did not rule out as-yet-undefined conditions capable of causing major reorganization of the IL-10 genomic locus of human neutrophils, thereby rendering it permissive to activation [206]. In this context, the authors of the study on IL-10–producing neutrophils suggested that, unlike LPS stimulation that promotes a pro-inflammatory neutrophil phenotype and blocks the chromatin modification at the IL-10 locus, LPS-stimulated Tregs induce chromatin modifications (H3K4me3, H3AcLys4) specific for transcriptionally active IL-10 gene in human neutrophils [204]. What also remains uncertain is the biological role of the subpopulation of IL-10–producing neutrophils in the periodontal pockets.…”

Section: Hyper-reactive and Suppressor Neutrophil Populations In Cmentioning

confidence: 99%

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Immune and regulatory functions of neutrophils in inflammatory bone loss

Hajishengallis

Moutsopoulos

Hajishengallis

et al. 2016

Seminars in Immunology

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Although historically viewed as merely anti-microbial effectors in acute infection or injury, neutrophils are now appreciated to be functionally versatile with critical roles also in chronic inflammation. Periodontitis, a chronic inflammatory disease that destroys the tooth-supporting gums and bone, is particularly affected by alterations in neutrophil numbers or function, as revealed by observations in monogenic disorders and relevant mouse models. Besides being a significant debilitating disease and health burden in its own right, periodontitis is thus an attractive model to dissect uncharted neutrophil-associated (patho)physiological pathways. Here, we summarize recent evidence that neutrophils can contribute to inflammatory bone loss not only through the typical bystander injury dogma but intriguingly also through their absence from the affected tissue, where they normally perform important immunomodulatory functions. Moreover, we discuss recent advances in the interactions of neutrophils with the vascular endothelium and – upon extravasation – with bacteria, and how the dysregulation of these interactions leads to inflammatory tissue damage. Overall, neutrophils have both protective and destructive roles in periodontitis, as they are involved in both the maintenance of periodontal tissue homeostasis and the induction of inflammatory bone loss. This highlights the importance of developing approaches that promote or sustain a fine balance between homeostatic immunity and inflammatory pathology.

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Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and IL-10

Cited by 79 publications

References 41 publications

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

Immune and regulatory functions of neutrophils in inflammatory bone loss

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