Regulation and Function of ILC3s in Pulmonary Infections

Hoffmann, Joseph P.; Kolls, Jay K.; McCombs, Janet E.

doi:10.3389/fimmu.2021.672523

Cited by 25 publications

(21 citation statements)

References 78 publications

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“…DCs also activate innate group 3 lymphoid cells (ILC3) during infection sustained by members of the Enterobacteriaceae family [40], producing a variety of cytokines, including IL-22 and IL-17A, and providing crucial protection against enteric pathogen infections.…”

Section: Discussionmentioning

confidence: 99%

Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect TH1/TH17 Response

et al. 2022

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Hypervirulent Klebsiella pneumoniae (Hv-Kp) strains have emerged as pathogens causing life-threatening, invasive disease even in immunocompetent hosts. Systemic dissemination usually occurs following perturbations of the gut microbiota and is facilitated by Hv-Kp resistance to phagocytosis and complement activity. Hv-Kp are usually associated with K1 or K2 capsular types, produce several iron uptake systems (e.g., aerobactin and salmochelin) and are often but not invariably, capsular material hyper-producers (hypermucoviscous phenotype: HMV). Whether Hv-Kp escape the immune response at mucosal site is unknown. In this work, we studied the effects of Hv-Kp on human dendritic cells (DCs), central players of the IL-23/IL-17 and IL-12/IFN-γ axis at mucosal sites, essential for pathogen clearance. Four Hv-Kp and HMV strains were selected and their activity on DC maturation and cytokine production was compared to that of non-virulent Kp strains with classic or HMV phenotypes. While the maturation process was equally induced by all Kp strains, significant differences between virulent and non-virulent strains were found in the expression of genes for cytokines involved in T-cell activation and differentiation. The non-virulent KP04C62 and the classic Kp, KPC157 induced high expression of TH1 (IL-12p70 and TNFα) and TH17 cytokines (IL-23, IL-1β and IL-6), while Hv-Kp poorly activated these cytokine genes. Moreover, conditioned media from DCs cultured with non-virulent Kp, either classical or hypercapsulated, induced the activation of IL-17 and IFN-γ genes in preactivated CD4+-cells suggesting their TH17/TH1 differentiation. Conditioned media from Hv-Kp poorly activated IL-17 and IFN-γ genes. In summary, our data indicate that Hv-Kp interfere with DC functions and T-cell differentiation and suggest that the escape from the IL-23/IL-17 and IL-12/IFN-γ axes may contribute to pathogen dissemination in immunocompetent hosts.

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Section: Discussionmentioning

confidence: 99%

Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect TH1/TH17 Response

et al. 2022

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“…In a recent review, Hoffmann et al. (2021) ( 36 ) showcased the corollary action of IL-17 in the airway’s viral infection and secondary bacterial infections ( 37 ). In this context, in association with IL-22, IL-17 can also regulate the function of the epithelial barrier and mediate host response to infections ( 38 – 40 ) by inducing the production of antimicrobial proteins and mucus, recruitment of monocytes and neutrophils, favoring tight junction formation, and the mucosal repair ( 41 – 44 ).…”

Section: Discussionmentioning

confidence: 99%

Distinct Immunological Profiles Help in the Maintenance of Salivary Secretory IgA Production in Mild Symptoms COVID-19 Patients

et al. 2022

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BackgroundRelevant aspects regarding the SARS-CoV-2 pathogenesis and the systemic immune response to this infection have been reported. However, the mucosal immune response of the upper airways two months after SARS-CoV-2 infection in patients with mild/moderate symptoms is still not completely described. Therefore, we investigated the immune/inflammatory responses of the mucosa of the upper airways of mild/moderate symptom COVID-19 patients two months after the SARS-CoV-2 infection in comparison to a control group composed of non-COVID-19 healthy individuals.MethodsA cohort of 80 volunteers (age 37.2 ± 8.2), including non-COVID-19 healthy individuals (n=24) and COVID-19 patients (n=56) who presented mild/moderate symptoms during a COVID-19 outbreak in Brazil in November and December of 2020. Saliva samples were obtained two months after the COVID-19 diagnosis to assess the levels of SIgA by ELISA and the cytokines by multiplex analysis.ResultsSalivary levels of SIgA were detected in 39 volunteers into the COVID-19 group and, unexpectedly, in 14 volunteers in the control group. Based on this observation, we distributed the volunteers of the control group into without SIgA or with SIgA sub-groups, and COVID-19 group into without SIgA or with SIgA sub-groups. Individuals with SIgA showed higher levels of IL-10, IL-17A, IFN-γ, IL-12p70, IL-13, and IFN-α than those without SIgA. In intergroup analysis, the COVID-19 groups showed higher salivary levels of IL-10, IL-13, IL-17A, and IFN-α than the control group. No statistical differences were verified in the salivary levels of IL-6 and IFN-β. Lower IL-12p70/IL-10 and IFN-γ/IL-10 ratios were found in the control group without SIgA than the control group with SIgA and the COVID-19 group with SIgA.ConclusionWe were able to present, for the first time, that associations between distinct immunological profiles can help the mucosal immunity to maintain the salivary levels of SIgA in COVID-19 patients two months after the SARS-CoV-2 infection.

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“…This finding is in line with its known role in bacterial infection. 33 The significant biomarkers for lupus pleuritis included the higher proportion of ANA positivity and lower levels of C4. Notably, ANA positivity achieved a high sensitivity of 91%, a specificity of 83%, a positive predictive value (PPV) of 59% and a high negative predictive value (NPV) of 97% in discriminating lupus pleuritis from pleural effusion of all other aetiologies combined (data not shown).…”

Section: Discussionmentioning

confidence: 99%

ANA positivity and complement level in pleural fluid are potential diagnostic markers in discriminating lupus pleuritis from pleural effusion of other aetiologies

et al. 2021

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ObjectiveLupus pleuritis is the most common pulmonary manifestation of systemic lupus erythematosus (SLE). We aimed to compare various biomarkers in discriminating between pleural effusions due to lupus pleuritis and other aetiologies.MethodsWe determined in 59 patients (16 patients with SLE and 43 patients without SLE) pleural fluid levels of high-mobility group box 1, soluble receptor for advanced glycation end products (sRAGE), adenosine deaminase (ADA), interleukin (IL) 17A, tumour necrosis factor-α, antinuclear antibodies (ANA), and complements C3 and C4.ResultsWe found significant differences in the pleural fluid level of sRAGE, ADA, IL-17A, C3 and C4, and in the proportion of ANA positivity, among lupus pleuritis and other groups with pleural effusion. Specifically, ANA positivity (titre ≥1: 80) achieved a high sensitivity of 91%, specificity of 83% and negative predictive value (NPV) of 97% in discriminating lupus pleuritis from non-lupus pleural effusion. A parallel combination of the level of C3 (<24 mg/dL) and C4 (<3 mg/dL) achieved a sensitivity of 82%, specificity of 89% and NPV of 93% in discriminating lupus pleuritis from non-lupus exudative pleural effusion.ConclusionsIn conclusion, ANA, C3 and C4 in pleural fluid are useful in discriminating lupus pleuritis from pleural effusion due to other aetiologies with high NPV.

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Regulation and Function of ILC3s in Pulmonary Infections

Cited by 25 publications

References 78 publications

Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect TH1/TH17 Response

Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect TH1/TH17 Response

Distinct Immunological Profiles Help in the Maintenance of Salivary Secretory IgA Production in Mild Symptoms COVID-19 Patients

ANA positivity and complement level in pleural fluid are potential diagnostic markers in discriminating lupus pleuritis from pleural effusion of other aetiologies

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