Dendritic cells in lung immunopathology

Cook, Peter C.; MacDonald, Andrew S.

doi:10.1007/s00281-016-0571-3

Cited by 62 publications

(55 citation statements)

References 175 publications

(200 reference statements)

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“…However, the potential mechanisms through which immune cells recognize fungal dysbiosis-derived signals to regulate distal allergic airway immune responses remain poorly characterized. We have recently shown that CX3CR1 + MNPs that express several antifungal receptors can efficiently recognize and uptake gut commensal fungi (Cook and MacDonald, 2016; Leonardi et al, 2018). Therefore, we next hypothesized that the direct sensing of fungi by gut CX3CR1 + MNPs might be responsible for the distal effects of fungal dysbiosis on systemic immunity and lung airway inflammation.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, we next hypothesized that the direct sensing of fungi by gut CX3CR1 + MNPs might be responsible for the distal effects of fungal dysbiosis on systemic immunity and lung airway inflammation. Since CX3CR1 + MNPs are an abundant cell type in both the gut and the lung, we developed a strategy allowing us to efficiently deplete CX3CR1 + MNPs in the gut without affecting lung CX3CR1 + MNPs or other cell types previously shown to play a role in allergic airway inflammation (Cook and MacDonald, 2016; Gibbings et al, 2017; Mionnet et al, 2010; Tweedle and Deepe, 2018) (Figure S4A-C, and Figure 3A). Specifically, we used diphtheria toxin (DT) injected intraperitoneally (i.p.)…”

Section: Resultsmentioning

confidence: 99%

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Response to Fungal Dysbiosis by Gut-Resident CX3CR1+ Mononuclear Phagocytes Aggravates Allergic Airway Disease

Leonardi

Semon

et al. 2018

Cell Host & Microbe

105

104

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Summary Sensing of the gut microbiota, including fungi, regulates mucosal immunity. Whether fungal sensing in the gut can influence immunity at other body sites is unknown. Here we show that fluconazole-induced gut fungal dysbiosis has persistent effects on allergic airway disease in a house dust mite challenge model. Mice with a defined community of bacteria, but lacking intestinal fungi were not susceptible to fluconazole-induced dysbiosis, while colonization with a fungal mixture recapitulated the detrimental effects. Gut resident mononuclear phagocytes (MNPs) expressing the fractalkine receptor CX3CR1 were essential for the effect of gut fungal dysbiosis on peripheral immunity. Depletion of CX3CR1+ MNPs or selective inhibition of Syk signaling downstream of fungal sensing in these cells ameliorated lung allergy. These results indicate that disruption of intestinal fungal communities can have persistent effects on peripheral immunity and aggravate disease severity through fungal sensing by gut resident CX3CR1+ MNPs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Response to Fungal Dysbiosis by Gut-Resident CX3CR1+ Mononuclear Phagocytes Aggravates Allergic Airway Disease

Leonardi

Semon

et al. 2018

Cell Host & Microbe

105

104

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“…38 The biological activation and function of DCs depends on pattern recognition receptors (PRRs) such as C-type lectin receptors, toll-like receptors (TLRs) and Nod-like receptors, as well as by cytokine and chemokine receptors. 39 DCs can respond to a variety of external antigens of microbial and non-microbial origin (bacterial, viral, fungal, protozoa, allergens, etc.) as well as damage-associated molecule patterns.…”

Section: Dcsmentioning

confidence: 99%

“…Ultimately, the combination of PRRs and other stimulated receptors determines subsequent activation of DCs. 39 …”

Section: Dcsmentioning

confidence: 99%

The Role of Forkhead Box 1 (FOXO1) in the Immune System: Dendritic Cells, T Cells, B Cells, and Hematopoietic Stem Cells

et al. 2017

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Forkhead box-O (FOXO) transcription factors have a fundamental role in the development and differentiation of immune cells. FOXO1 and FOXO3 are FOXO members that are structurally similar and bind to the same conserved consensus DNA sequences to induce transcription. FOXO1 has been studied in detail in the activation of dendritic cells (DCs), where it plays an important role through the regulation of target genes such as ICAM-1, CCR7, and the integrin αvβ3. FOXO1 is activated by bacteria challenge in DCs and promotes DC bacterial phagocytosis, migration, homing to lymph nodes, DC stimulation of CD4+ T cells and resting B cells, and antibody production. Deletion of FOXO1 in DCs enhances susceptibility to bacteria-induced periodontal disease. FOXO1 and FOXO3 maintain naive T cell quiescence and survival. FOXO1 and FOXO3 enhance the formation of regulatory T cells and inhibit the formation of T-helper 1 (Th1) and Th17 cells. FOXO1 promotes differentiation, proliferation, survival, immunoglobulin gene rearrangement, and class switching in B cells, but FOXO3 has little effect. Both FOXO1 and FOXO3 are important in the maintenance of hematopoietic stem cells by protecting them from oxidative stress. This review examines FOXO1/FOXO3 in the adaptive immune response, key target genes, and FOXO inhibition by the phosphoinositide 3-kinase/AKT pathway.

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“…For example, a microenvironment rich in IL-12 will lead to the activation and differentiation of natural killer (NK) lymphocytes. 22 It has recently been proposed that COPD may be an entity of autoimmune etiology, because autoantibodies have been found against peptides present in the extracellular matrix of lung tissue. Among them, the most important is elastin (anti-elastin antibodies are then formed).…”

Section: Adaptive Immunitymentioning

confidence: 99%

Th17 profile in COPD exacerbations

Ponce-Gallegos¹,

Ramírez‐Venegas²,

Falfán-Valencia³

2017

COPD

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COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow. It is mainly associated with exposure to cigarette smoke. In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide. Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells. Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways. The aims of these molecules are differentiation, proliferation and recruitment of neutrophils. Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight. In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract. Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity.

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Dendritic cells in lung immunopathology

Cited by 62 publications

References 175 publications

Response to Fungal Dysbiosis by Gut-Resident CX3CR1+ Mononuclear Phagocytes Aggravates Allergic Airway Disease

Response to Fungal Dysbiosis by Gut-Resident CX3CR1+ Mononuclear Phagocytes Aggravates Allergic Airway Disease

The Role of Forkhead Box 1 (FOXO1) in the Immune System: Dendritic Cells, T Cells, B Cells, and Hematopoietic Stem Cells

Th17 profile in COPD exacerbations

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