European journal of immunology
-
Acute inflammation is the pathophysiological basis of important clinical conditions associated with organ failure. The initial inflammatory response is controlled by the chemokine system, yet recent data have indicated that the neuronal guidance cues are significantly involved in the orchestration of this process. Previous work has shown the proinflammatory capacity of the guidance cue semaphorin (Sema) 7a, but the role of one of its target receptors, the plexin C1 (PLXNC1) receptor is to date unknown. ⋯ To probe the therapeutic potential of PLXNC1 we treated C57BL/6 WT mice with an anti-PLXNC1 antibody and a PLXNC1 binding peptide. Both of these interventions significantly dampened ZyA-induced peritonitis. These results implicate an important role of PLXNC1 during an acute inflammatory response and indicate PLXNC1 as a potential target for the control of conditions associated with acute inflammation.
-
Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis that is responsible for almost 1.5 million deaths per year. Sensing of mycobacteria by the host's immune system relies on different families of receptors present on innate immune cells. Amongst them, several members of the TLR family are involved in the activation of immune cells by mycobacteria, yet the in vivo contribution of individual TLRs to the protective immune response remains controversial. ⋯ MyD88 is expressed in both immune and non-immune cells, but it is not clear whether control of mycobacteria requires ubiquitous or cell-type specific MyD88 expression. Therefore, using novel conditional switch-on mouse models, we aimed to investigate the importance of MyD88 signalling in DCs and macrophages for the induction of protective effector mechanisms against mycobacterial infection. We conclude that specific reactivation of MyD88 signalling in CD11c- or lysozyme M-expressing myeloid cells during Mycobacterium bovis Bacille Calmette-Guerin infection is sufficient to restore systemic and local inflammatory cytokine production and to control pathogen burden.
-
Randomized Controlled Trial
Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome.
The HIV-TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can complicate combined treatments for HIV-1 and TB. Little is known about tissue damage in TB-IRIS. Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and consequently may play a role in such immunopathology. ⋯ Serum MMP-7 concentration was elevated in TB-IRIS and 2 weeks of corticosteroid therapy decreased this level, although not significantly. TB-IRIS is associated with a distinct pattern of MMP gene and protein activation. Modulation of dysregulated MMP activity may represent a novel therapeutic approach to alleviate TB-IRIS in HIV-TB patients undergoing treatment.
-
Chronic asthma is an inflammatory disease of the airway wall that leads to bronchial smooth muscle hyperreactivity and airway obstruction, caused by inflammation, goblet cell metaplasia, and airway wall remodeling. In response to allergen presentation by airway DCs, T-helper lymphocytes of the adaptive immune system control many aspects of the disease through secretion of IL-4, IL-5, IL-13, IL-17, and IL-22, and these are counterbalanced by cytokines produced by Treg cells. ⋯ Barrier epithelial cells are being ever more implicated in disease pathogenesis than previously thought, as these cells have in recent years been shown to sense exposure to allergens via pattern recognition receptors and to activate conventional and inflammatory-type DCs and other innate immune cells through the secretion of thymic stromal lymphopoietin, granulocyte-macrophage colony stimulating factor, IL-1, IL-33, and IL-25. Understanding this cytokine crosstalk between barrier epithelial cells, DCs, and immune cells provides important insights into the mechanisms of allergic sensitization and asthma progression as discussed in this review.
-
Th17 cytokines can play both protective and pathologic roles in the airways. An emerging theme in Th17 cytokine biology is that these responses can mediate tissue pathology when downstream effector cells are dysfunctional, such as neutrophils lacking functional NADPH oxidase in the case of chronic granulomatous disease, or epithelial cells lacking appropriate ion transport as in the case of cystic fibrosis. In this Mini-Review we highlight recent advances in the protective and pathologic roles of Th17 cytokines in the context of infection at the pulmonary barrier.