Monocyte-derived macrophages (Mφs) are crucial regulators during muscularis inflammation. However, it is unclear which micro-environmental factors are responsible for monocyte recruitment and ...anti-inflammatory Mφ differentiation in this paradigm. Here, we investigate Mφ heterogeneity at different stages of muscularis inflammation and determine how environmental cues can attract and activate tissue-protective Mφs. Results showed that muscularis inflammation induced marked alterations in mononuclear phagocyte populations associated with a rapid infiltration of Ly6c
monocytes that locally acquired unique transcriptional states. Trajectory inference analysis revealed two main pro-resolving Mφ subpopulations during the resolution of muscularis inflammation, i.e. Cd206
MhcII
and Timp2
MhcII
Mφs. Interestingly, we found that damage to the micro-environment upon muscularis inflammation resulted in EGC activation, which in turn stimulated monocyte infiltration and the consequent differentiation in anti-inflammatory CD206
Mφs via CCL2 and CSF1, respectively. In addition, CSF1-CSF1R signaling was shown to be essential for the differentiation of monocytes into CD206
Mφs and EGC proliferation during muscularis inflammation. Our study provides a comprehensive insight into pro-resolving Mφ differentiation and their regulators during muscularis inflammation. We deepened our understanding in the interaction between EGCs and Mφs, thereby highlighting pro-resolving Mφ differentiation as a potential novel therapeutic strategy for the treatment of intestinal inflammation.
Conventional dendritic cells (DCs) are considered to be the prime initiators of airway allergy. Yet, it remains unclear whether specific DC subsets are preferentially involved in allergic airway ...sensitization. Here, we systematically assessed the respective pro-allergic potential of individually sorted lung DC subsets isolated from house dust mite antigen (HDM)-treated donor mice, following transfer to naïve recipients. Transfer of lung CD11c(+)CD11b(+) DCs, but not CD11c(+)CD11b(-)CD103(+) DCs, was sufficient to prime airway allergy. The CD11c(+)CD11b(+) DC subpopulation was composed of CD11c(+)CD11b(+)Ly6C(+) inflammatory monocyte-derived cells, whose numbers increase in the lungs following HDM exposure, and of CD11c(+)CD11b(+)Ly6C(-) DCs, which remain stable. Counterintuitively, only CD11c(+)CD11b(+)Ly6C(-) DCs, and not CD11c(+)CD11b(+)Ly6C(+) DCs, were able to convey antigen to the lymph nodes and induce adaptive T cell responses and subsequent airway allergy. Our results thus support that lung resident non-inflammatory CD11c(+)CD11b(+)Ly6C(-) DCs are the essential inducers of allergic airway sensitization to the common aeroallergen HDM in mice.
Background Pattern-recognition receptors (PRRs) are critically involved in the pathophysiology of airway allergy, yet most of the signaling pathways downstream of PRRs implicated in allergic airway ...sensitization remain unknown. Objective We sought to study the effects of genetic depletion of interferon response factor (IRF) 3 and IRF7, important transcription factors downstream of various PRRs, in a murine model of house dust mite (HDM)–induced allergic asthma. Methods We compared HDM-induced allergic immune responses in IRF3-deficient (IRF3−/− ), IRF7−/− , and wild-type mice. Results Parameters of airway allergy caused by HDM exposure were strongly attenuated in IRF3−/− , but not IRF7−/− , mice compared with those in wild-type mice. Indeed, in HDM-exposed IRF3−/− mice HDM-specific TH 2 cell responses did not develop. This correlated with impaired maturation and migration of IRF3−/− lung dendritic cells (DCs) on HDM treatment. Furthermore, adoptive transfer of HDM-loaded DCs indicated that IRF3−/− DCs had an intrinsic defect rendering them unable to migrate and to prime HDM-specific TH 2 responses. Intriguingly, we also show that DC function and allergic airway sensitization in response to HDM were independent of signaling by type I interferons, the main target genes of IRF3. Conclusion Through its role in DC function, IRF3, mainly known as a central activator of antiviral immunity, is essential for the development of TH 2-type responses to airway allergens.
Role of neutrophils in allergic asthma Radermecker, Coraline; Louis, Renaud; Bureau, Fabrice ...
Current opinion in immunology,
10/2018, Letnik:
54
Journal Article, Web Resource
Recenzirano
Odprti dostop
The contribution of neutrophils to asthma pathogenesis has been mainly studied in the context of non-allergic neutrophilic asthma. However, neutrophils can also be rapidly recruited and are largely ...present in the airways of allergic eosinophilic asthmatic patients. Under these circumstances, they possess specific phenotypic features distinguishing them from resting blood neutrophils and are endowed with particular functions. The exact contribution of neutrophils to allergic asthma pathogenesis is still unclear, but growing experimental evidence supports the ability of neutrophils or neutrophil-derived products to influence the underlying allergic type 2 immune response and cardinal features of allergic asthma, thus shedding new light on neutrophil biology and functions in an allergic context.
Influenza A virus (IAV) infections pose a global health challenge that necessitates a comprehensive understanding of the host immune response to devise effective therapeutic interventions. As ...monocytes and macrophages play crucial roles in host defence, inflammation, and repair, this review explores the intricate journey of these cells during and after IAV infection. First, we highlight the dynamics and functions of lung-resident macrophage populations post-IAV. Second, we review the current knowledge of recruited monocytes and monocyte-derived cells, emphasising their roles in viral clearance, inflammation, immunomodulation, and tissue repair. Third, we shed light on the consequences of IAV-induced macrophage alterations on long-term lung immunity. We conclude by underscoring current knowledge gaps and exciting prospects for future research in unravelling the complexities of macrophage responses to respiratory viral infections.
PDF
