Activation Of Innate Lymphoid Cells Research Articles

Innate lymphoid cell composition associates with COVID-19 disease severity.

ObjectivesThe role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is unknown. Understanding the immune response in COVID‐19 could contribute to unravel the pathogenesis and identification of treatment targets. Here, we describe the phenotypic landscape of circulating ILCs in COVID‐19 patients and identified ILC phenotypes correlated to serum biomarkers, clinical markers and laboratory parameters relevant in COVID‐19.MethodsBlood samples collected from moderately (n = 11) and severely ill (n = 12) COVID‐19 patients, as well as healthy control donors (n = 16), were analysed with 18‐parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID‐19 patients, and serum biomarkers were analysed with multiplex immunoassays.ResultsInnate lymphoid cells were largely depleted from the circulation of COVID‐19 patients compared with healthy controls. Remaining circulating ILCs revealed decreased frequencies of ILC2 in severe COVID‐19, with a concomitant decrease of ILC precursors (ILCp) in all patients, compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID‐19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity.ConclusionThis study provides insights into the potential role of ILCs in immune responses against SARS‐CoV‐2, particularly linked to the severity of COVID‐19.

Iloprost inhibits acute allergic nasal inflammation by GATA3 -ILC2 pathway in mice

BackgroundAcute allergic nasal inflammation is very common in the clinical allergic diseases, Prostaglandin I2 (PGI2) has been found to effective in combating inflammation. Iloprost, as an analog of PGI2, whose role and mechanisms in the acute allergic nasal inflammation remains unclear. It’s necessary to elucidate the efficacy and potential mechanism of Iloprost in acute allergic nasal inflammation. Methods36 female mice were randomly divided into DMSO group, IL 33 group, Iloprost group and IL 33+Iloprost intervention group. Mice were stimulated with IL 33 to construct an acute allergic nasal inflammation model. Hematoxylin and eosin (HE) and periodic acid Schiff reagent (PAS) staining, flow cytometry, Real time PCR and Enzyme linked immunosorbent assay (ELISA) was used to identify the role of Iloprost in acute allergic nasal inflammation. The comparison between multiplied groups was analyzed by ANOVA, and the Bonferroni method was used for further comparison of two groups. ResultsCompared with IL 33 group, the inflammatory cell infiltration around the trachea and blood vessels of the lung tissue in the IL 33+ Iloprost group were reduced; goblet cell hyperplasia was observed in airway mucosa of IL 33 group, and the mucus secretion increased; the percentage of EOS and ILC2s in the BALF and lung single cell suspensions in IL 33+ Iloprost group were statistically lower than that of IL 33 group (p < 0.05); The mRNA expression levels of IL 5, IL 13, ST2 and GATA3 in the lung tissue of IL 33 group were higher than those in DMSO group (p < 0.05). After intervention with Iloprost, the mRNA expression levels of IL 5, IL 13, GATA3 and ST2 were lower than those in IL 33 group (p < 0.05) ConclusionIloprost may potentially inhibit the proliferation and activation of innate lymphoid cells 2 in mice with acute allergic inflammation, which maybe an effective option for the treatment of acute allergic inflammation related diseases.

Mucosal-associated invariant T cells restrict allergic airway inflammation

We report that MAIT cells repress group 2 innate lymphoid cell activation and restrict allergen-induced airway inflammation and airway hyperresponsiveness.

A three course menu for ILC and bystander T cell activation.

The varied list of agonists that activate innate lymphoid cells (ILCs) continues to grow, but whether and how these signals interact is not well defined, especially in vivo. ILC subsets share master transcription factors, chromatin landscapes, and effector cytokines with their corresponding T helper (Th) cell subsets. Here we discuss how studies of these two cell types can inform each other. Specifically, we outline a framework in which ILC agonists are grouped by the transcription factors they activate. Optimal ILC activation requires at least three items from a 'menu' of non-redundant signals that collectively replicate the STAT and TCR signaling that drives effector Th cell function. This conceptual model may also apply to TCR-independent 'bystander' activation of Th cells.

The role of innate lymphoid cells and T helper cell activation in type 2 diabetic patients: a protocol for a systematic review and meta-analysis

BackgroundPersistent levels of low-grade inflammation and T lymphocyte activation are associated with insulin resistance and type 2 diabetes that eventually lead to the development of cardiovascular diseases. Interestingly, increasing studies report on an emerging role of innate lymphoid cells in the development of both type 2 diabetes and cardiovascular disease. This systematic review will provide a comprehensive synthesis of available studies reporting on the role of innate lymphoid cells and associated T helper cell function in type 2 diabetic patients. It will further provide insight into the association of innate lymphoid cell activation and cardiovascular risk in adults living with type 2 diabetes.MethodsThis systematic review protocol has been prepared in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines. The protocol has been registered with PROSPERO (CRD42018106159). This systematic review and meta-analysis will include published randomised clinical trials, observational studies, and case-control studies. We will also include grey literature. A search strategy will be developed with the help of subject librarian using Medical Subject Heading (MeSH) words for MEDLINE. This will then be adapted for the Embase database. Two independent reviewers VM and BBN will screen all studies using prespecified inclusion and exclusion criteria. The Downs and Black checklist will be used to assess the quality of individual studies. Predefined relevant data items will be extracted using sheets, and all study tables will be created using Review Manager V.5.3. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the strength of evidence.Ethics and disseminationThe review will include publicly available data. The findings of this review will be disseminated through publications.

IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection

Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.

Mechanical Skin Injury Promotes Food Anaphylaxis by Driving Intestinal Mast Cell Expansion

Mast cell (MC) mediator release after crosslinking of surface-bound IgE antibody by ingested antigen underlies food allergy. However, IgE antibodies are not uniformly associated with food allergy, and intestinal MC load is an important determinant. Atopic dermatitis (AD), characterized by pruritis and cutaneous sensitization to allergens, including foods, is strongly associated with food allergy. Tape stripping mouse skin, a surrogate for scratching, caused expansion and activation of small intestinal MCs, increased intestinal permeability, and promoted food anaphylaxis in sensitized mice. Tape stripping caused keratinocytes to systemically release interleukin-33 (IL-33), which synergized with intestinal tuft-cell-derived IL-25 to drive the expansion and activation of intestinal type-2 innate lymphoid cells (ILC2s). These provided IL-4, which targeted MCs to expand in the intestine. Duodenal MCs were expanded in AD. In addition to promoting cutaneous sensitization to foods, scratching may promote food anaphylaxis in AD by expanding and activating intestinal MCs.

Group 3 ILCs: Peacekeepers or Troublemakers? What's Your Gut Telling You?!

A complex network of interactions exists between the microbiome, the epithelium, and immune cells that reside along the walls of the gastrointestinal tract. The intestinal immune system has been assigned with the difficult task of discriminating between commensal, harmless bacteria, and invading pathogens that translocate across the epithelial monolayer. Importantly, it is trained to maintain tolerance against commensals, and initiate protective immune responses against pathogens to secure intestinal homeostasis. Breakdown of this fine balance between the host and its intestinal microbiota can lead to intestinal inflammation and subsequently to development of inflammatory bowel disease (IBD). A decade since their discovery, innate lymphoid cells (ILCs) are now recognized as important regulators of intestinal homeostasis. ILC3s have emerged as a critical subset in the gut. They are the most phenotypically diverse ILC population and interact directly with numerous different cell types (haematopoietic and non-haematopoeitic), as well as interface with the bacterial flora. In addition to their contribution to intestinal pathogen immunity, they also mitigate against tissue damage occurring following acute injury, by facilitating tissue repair and regeneration, a key function in the maintenance of intestinal homeostasis. However, in chronic inflammation the tables are turned and ILC3s may acquire a pro-inflammatory phenotype in the gut. Chronic ILC activation can lead to persistent inflammation contributing to IBD and/or colorectal cancer. In this review, we discuss current knowledge of group 3 ILCs and their contributions to intestinal homeostasis and disease leading to novel therapeutic targets and clinical approaches that may inform novel treatment strategies for immune-mediated disorders, including IBD.

Cutting Edge: Core Binding Factor β Is Required for Group 2 Innate Lymphoid Cell Activation.

Group 2 innate lymphoid cells (ILC2) are tissue-resident, long-lived innate effector cells implicated in allergy and asthma. Upon activation, mature ILC2 rapidly secrete large amounts of type-2 cytokines and other effector molecules. The molecular pathways that drive ILC2 activation are not well understood. In this study, we report that the transcriptional controller core binding factor β (CBFβ) is required for ILC2 activation. Deletion or inhibition of CBFβ did not impair the maintenance of ILC2 at homeostasis but abolished ILC2 activation during allergic airway inflammation. Treatment with CBFβ inhibitors prevented ILC2-mediated airway hyperresponsiveness in a mouse model of acute Alternaria allergen inhalation. CBFβ promoted expression of key ILC2 genes at both transcriptional and translational levels. CBF transcriptional complex directly bound to Il13 and Vegfa promoters and enhancers, and controlled gene transcription. CBFβ further promoted ribosome biogenesis and enhanced gene translation in activated ILC2. Together, these data establish an essential role for CBFβ in ILC2 activation.

Negative regulation of innate lymphoid cell responses in inflammation and cancer

The immune system employs an array of effector cells to ensure tissue homeostasis and protection against pathogens. Lymphocytes belonging to both the adaptive and innate branches share several functions, comprising the ability to directly kill stressed or transformed cells, and to provide helper responses through specific production of cytokines. These properties are regulated by distinct sets of soluble molecules, receptors, and intracellular factors, which altogether tune the functional output of effector lymphocytes and their final activation state. In contrast to adaptive T cells, innate lymphoid cells (ILCs) do not require antigen receptors and are characterized for their ability to provide rapid immune responses. While the factors underlying functional diversification and the main principles leading to ILC activation have been dissected, our understanding of the mechanisms underlying termination of ILC effector functions is still in its infancy. Herein, we discuss the recent findings describing how ILC responses are turned off in the context of inflammation and cancer.

IL-25-regulated type 2 innate lymphoid cells activation promote allergic fungal rhinosinusitis

Objective: To investigate the regulation of IL-25 on type Ⅱ innate lymphoid cells (ILC2s) activation in the pathogenesis of allergic fungal rhinosinusitis (AFRS). Methods: Nasal mucosa tissues were collected from 16 AFRS patients and 12 patients, who underwent nasal endoscopic surgery for cerebrospinal rhinorrhea or skull base benign tumor during the period from June 2016 to June 2017 in Department of Rhinology, the First Affiliated Hospital of Zhengzhou University. Firstly, flow cytometry was used to detect ILC2s in nasal mucosa of both groups. Secondly, the expression of IL-25, IL-5 and IL-13 in nasal mucosa was detected by immunofluorescence and/or Western Blot assay. Finally, fungal extracts, IL-25 and glucocorticoids were used to stimulate nasal mucosal epithelial cells and tissues in vitro respectively to detect the regulatory effect of IL-25 on ILC2s. SPSS 16.0 software was used to analyze the data. Results: The prevalence of ILC2s in nasal tissues was higher in patients with AFRS than those of the control group ((3.85±1.52)%(Mean±SD) vs (0.32±0.10)%, U=9.00, P<0.05). There was a positive correlation between the prevalence of ILC2s and the number of eosinophils in nasal mucosa of patients with ARFS (r=0.80, P<0.05). The expression of IL-25, IL-5 and IL-13 in nasal mucosa epithelium of AFRS group was significantly higher than that of the control group (0.49±0.13 vs 0.23±0.09, 0.23±0.05 vs 0.10±0.04, 0.31±0.08 vs 0.14±0.07, t value was 5.90, 7.21, 5.69, respectively, all P<0.05). Fungal stimulation enhanced the expression of IL-25 protein in nasal epithelial cells of both groups (0.67±0.19 vs 0.25±0.12 (AFRS group), 0.62±0.17 vs 0.27±0.16 (control group), q value was 8.65, 9.26, respectively, all P<0.05). In the IL-25 stimulated nasal mucosa at a concentration of 1, 10 and 100 ng/ml, the expression level of retinoid acid-related orphan receptor α (RORα) mRNA was 2.07±1.53, 5.06±0.93, 7.38±2.30, respectively; the expression level of GATA binding protein 3 (GATA3) mRNA was 3.58±1.29, 6.14±1.55, 7.64±2.28, respectively; the expression level of IL-5 protein was 0.21±0.06, 0.32±0.06, 0.38±0.10, respectively; the expression level of IL-13 was 0.52±0.13, 0.69±0.22, 0.82±0.21, respectively, which were significantly higher than that in the unstimulated nasal mucosa (1.00±0.00, 1.00±0.00, 0.11±0.05, 0.35±0.15, F value was 63.45, 59.27, 49.35, 20.20, respectively, all P<0.05). The up-regulation could be inhibited by dexamethasone (F value was 89.20, 92.47, 99.63, 49.82, respectively, all P<0.05). Conclusions: Epithelial-derived IL-25 up-regulates the expression of IRC2s-dependent transcription factors RORα and GATA3 mRNA, which are positively correlated with elevated IL-13 and IL-5 expression levels in tissues, may be involved in AFRS inflammatory response, and are inhibited by glucocorticoids.

Cytokine-induced endogenous production of prostaglandin D2 is essential for human group 2 innate lymphoid cell activation

Group 2 innate lymphoid cells (ILC2s) play a key role in the initiation and maintenance of type 2 immune responses. The prostaglandin (PG) D2-chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) receptor axis potently induces cytokine production and ILC2 migration. We set out to examine PG production in human ILC2s and the implications of such endogenous production on ILC2 function. The effects of the COX-1/2 inhibitor flurbiprofen, the hematopoietic prostaglandin D2 synthase (HPGDS) inhibitor KMN698, and the CRTH2 antagonist CAY10471 on human ILC2s were determined by assessing receptor and transcription factor expression, cytokine production, and gene expression with flow cytometry, ELISA, and quantitative RT-PCR, respectively. Concentrations of lipid mediators were measured by using liquid chromatography-tandem mass spectrometry and ELISA. We show that ILC2s constitutively express HPGDS and upregulate COX-2 upon IL-2, IL-25, and IL-33 plus thymic stromal lymphopoietin stimulation. Consequently, PGD2 and its metabolites can be detected in ILC2 supernatants. We reveal that endogenously produced PGD2 is essential in cytokine-induced ILC2 activation because blocking of the COX-1/2 or HPGDS enzymes or the CRTH2 receptor abolishes ILC2 responses. PGD2 produced by ILC2s is, in a paracrine/autocrine manner, essential in cytokine-induced ILC2 activation. Hence we provide the detailed mechanism behind how CRTH2 antagonists represent promising therapeutic tools for allergic diseases by controlling ILC2 function.

The regenerating family member 3 β instigates IL-17A-mediated neutrophil recruitment downstream of NOD1/2 signalling for controlling colonisation resistance independently of microbiota community structure

ObjectiveLoss of the Crohn’s disease predisposing NOD2 gene results in an intestinal microenvironment conducive for colonisation by attaching-and-effacing enteropathogens. However, it remains elusive whether it relies on the intracellular recruitment...

Unique Cytokine Profile of Novel Innate Lymphoid Cells in Human Decidua

Abstract Immune cells at the maternal-fetal interface play a complex role in regulation of vascular remodeling, fetal tolerance and protection from infection. We have previously presented the identification of two novel CD56highNKs based on Eomes expression (Eomeslo/hi). Activation of these subsets revealed preferential production of IL-8 and IL-17A by decidual innate lymphoid cells (ILCs). Decidual specimens were dissected from term placentas and mononuclear cells (MCs) were isolated by mechanical (GentleMACS) and enzymatic (Collagenase, DNAse) disruption. MCs were then simulated with PMA/ionomycin or IL-23, then labeled by flurochrome-conjugate antibodies against surface CD3, 14, 16, 19, 34, 45, 49a, 56, 94, 117, 127, 335 and intracellular Granzyme B, IL-8, IL-17A, IL-22, INFγ, TNFα. Data acquisition was performed using BD Fortessa flow cytometer in a 5 laser, 18 detector configuration and data analysis was performed using FlowJo 10.2. Activation of decidual ILCs revealed a unique milieu of cytokine production. The novel subsets, CD56high Eomeslo/hi, preferentially produced IL-8 and IL-17A, while decreasing production of INFγ, Granzyme B, and TNFα. In addition, as expected, ILC3s and LTi-like cells produced IL-17A and IL-22. Furthermore, differences in response were observed between decidual basalis and decidual parietalis ILCs, with decidual parietalis ILCs being more responsive to stimulation. Preliminary results suggest that both CD56high Eomeslo/hi subsets demonstrate a similar altered cytokine profile that is conducive to decidual remodeling. Further gene expression analysis will reveal if these novel subsets represent a truly unique population or are members of the expanding tissue-resident NK cell family.

Leukotriene C4 Potentiates IL-33-Induced Group 2 Innate Lymphoid Cell Activation and Lung Inflammation.

Asthma is a complex disease that is promoted by dysregulated immunity and the presence of many cytokine and lipid mediators. Despite this, there is a paucity of data demonstrating the combined effects of multiple mediators in asthma pathogenesis. Group 2 innate lymphoid cells (ILC2s) have recently been shown to play important roles in the initiation of allergic inflammation; however, it is unclear whether lipid mediators, such as cysteinyl leukotrienes (CysLTs), which are present in asthma, could further amplify the effects of IL-33 on ILC2 activation and lung inflammation. In this article, we show that airway challenges with the parent CysLT, leukotriene C4 (LTC4), given in combination with low-dose IL-33 to naive wild-type mice, led to synergistic increases in airway Th2 cytokines, eosinophilia, and peribronchial inflammation compared with IL-33 alone. Further, the numbers of proliferating and cytokine-producing lung ILC2s were increased after challenge with both LTC4 and IL-33. Levels of CysLT1R, CysLT2R, and candidate leukotriene E4 receptor P2Y12 mRNAs were increased in ILC2s. The synergistic effect of LTC4 with IL-33 was completely dependent upon CysLT1R, because CysLT1R-/- mice, but not CysLT2R-/- mice, had abrogated responses. Further, CysLTs directly potentiated IL-5 and IL-13 production from purified ILC2s stimulated with IL-33 and resulted in NFAT1 nuclear translocation. Finally, CysLT1R-/- mice had reduced lung eosinophils and ILC2 responses after exposure to the fungal allergen Alternaria alternata Thus, CysLT1R promotes LTC4- and Alternaria-induced ILC2 activation and lung inflammation. These findings suggest that multiple pathways likely exist in asthma to activate ILC2s and propagate inflammatory responses.

The Role of Innate Lymphoid Cells in Immune-Mediated Liver Diseases.

Innate lymphoid cells (ILCs) are a recently identified group of innate immune cells lacking antigen-specific receptors that can mediate immune responses and regulate tissue homeostasis and inflammation. ILCs comprise group 1 ILCs, group 2 ILCs, and group 3 ILCs. These ILCs usually localize at mucosal surfaces and combat pathogens by the rapid release of certain cytokines. However, the uncontrolled activation of ILCs can also lead to damaging inflammation, especially in the gut, lung, and skin. Although the physiological and pathogenic roles of ILCs in liver diseases have been attracting increasing attention recently, there has been no systematic review regarding the roles of ILCs in immune-mediated liver diseases. Here, we review the relationships between the ILC subsets and their functions in immune-mediated liver diseases, and discuss their therapeutic potential based on current knowledge about the functional roles of these cells in liver diseases.

The relationship between the cytokines TNF and TL1A in rheumatoid arthritis

Abstract The TNF-family cytokine TL1A (TNF-like ligand 1A) signaling through its receptor DR3 (Death Receptor 3) promotes immunopathology in diverse autoimmune disease models by facilitating T cell accumulation and Innate Lymphoid Cell activation at the site of inflammation while leaving systemic immune responses unaffected. TNF, a close homolog of TL1A, is a successful therapeutic in autoimmune diseases including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, a significant fraction of patients do not adequately respond to TNF blockade and are in need of alternative therapies. Previous studies have reported elevated TL1A levels in serum and synovial fluid of patients with RA. Yet, how TL1A expression may be influenced by TNF, and whether blocking TL1A/DR3 interactions would be a viable treatment for RA is unknown. We found that soluble TL1A levels are specifically elevated in synovial fluid and serum from RA patients, and that TNF blockade reduces serum TL1A levels in both responders and non-responders. Additionally, in a murine model of collagen-induced arthritis, antibody blockade of TL1A reduced both clinical disease and bone destruction. To further understand the relationship between TL1A and TNF we are now utilizing the TNFDARE mouse model of spontaneous TNF driven arthritis crossed to DR3 deficient mice. By 3D micro CT imaging and cytokine analysis of the joints we will determine if the blockade of TL1A/DR3 interactions alleviates arthritis driven by excess TNF. Taken together, these studies support an investigation into TL1A blockade as a potential therapy for patients with rheumatoid arthritis.

‘The role of leukocyte NADPH oxidase in the regulation of IL-1 family cytokines and innate lymphoid cells in serum-induced arthritis.’

Abstract Innate lymphoid cells (ILCs) have been recently identified in different tissues as an important class of innate immune cells involved in the inflammatory response during health and disease. Our previous studies showed that reactive oxygen species (ROS) act as negative feedback to regulate IL-1β-mediated inflammation, accounting for the more severe arthritis in the absence of leukocyte NADPH oxidase (NOX2), which is responsible for producing most of the ROS in inflammatory tissues. In this study, we set out to identify and characterize innate lymphoid cells in the arthritic joints based on the hypothesis that leukocyte-produced ROS are critical for modulating innate lymphoid cells activation and IL-1 family cytokines production in serum induced arthritis. We found that serum-induced joint inflammation may be more severe and induce higher IL-1β, IL-18 but less IL-33 cytokines expression and a population of lineage-negative CD45 positive cells was identified in the synovial fluid and tissue of diseased joints. Comparison of ILC populations between WT and Ncf1−/− arthritic mice showed that ILC2 and NCR posetive ILC3 were more abundant in the joint of NOX2 deficient mice. Moreover, the phagocytic NADPH oxidase was an essential regulator of ILC3 populations switching in the inflammatory tissues of arthritis. Given the fact that these cells are capable of rapid cytokine production and leukocyte-produced ROS appear to affect these ILC populations, our ongoing investigations promise to reveal novel redox-sensitive immunoregulatory mechanisms mediated by ILC through IL-1 family cytokines.

Inhibition of Innate Lymphoid Cell Activation by Interleukin-23 Secreting Dendritic Cells During Bordetella pertussis Infections in Mice

Abstract Bordetella pertussis (B. pertussis), the causative agent of whooping cough, is a highly contagious respiratory tract disease marked by extensive damage to the mucosal lining and a delay in immune response due to the pertussis toxin (PTX). In this study, the focus is on the characteristics and mechanisms of two innate immune cell populations, the IL-23-secreting dendritic cells (DCs) and the IL-22-secreting innate lymphoid cells (ILCs). We hypothesize that infection with B. pertussis interferes with the IL-23/IL-22 axis pathway due to PTX production. We compared these immune responses in mice models of whooping cough, triggered by B. pertussis (prolonged disease) or Bordetella parapertussis (B. parapertussis) – an acute version of the infection, lacking PTX. Flow cytometry studies show an increased in lung DCs at 2dpi with B. parapertussis compared to B. pertussis and uninfected mice. At 2dpi with B. parapertussis, more lung CD11b+ DC at secrete IL-23 compare to B. pertussis. The percentage of ILC3 is equally increased at 2dpi with B. pertussis and B. parapertussis-infected mice. Proliferation analyses suggest that residential ILCs proliferate locally rather then recruited during infection to the lungs. Despite the increase in IL-23-producing DCs, no differential expression of IL-22 by ILC3 was observed between infections and uninfected mice. Further studies would verify the nature of this inhibition and whether it is translated to a reduced level of antimicrobial substances secreted by lung epithelial cells. The outcomes of this study may clarify the inability of these innate immune responses to resolve B. pertussis infection early.

Group 2 innate lymphoid cell activation in the neonatal lung drives type 2 immunity and allergen sensitization

Group 2 innate lymphoid cell activation in the neonatal lung drives type 2 immunity and allergen sensitization