scholarly journals Secreted Phospholipase A2 Group X Acts as an Adjuvant for Type 2 Inflammation, Leading to an Allergen-Specific Immune Response in the Lung

2020 ◽  
Vol 204 (12) ◽  
pp. 3097-3107 ◽  
Author(s):  
Herbert Luke Ogden ◽  
Ying Lai ◽  
James D. Nolin ◽  
Dowon An ◽  
Charles W. Frevert ◽  
...  
Keyword(s):  
Immune Response ◽  
Phospholipase A2 ◽  
Specific Immune Response ◽  
Secreted Phospholipase A2 ◽  
Type 2 Inflammation

scholarly journals Lipid Profile of Activated Macrophages and Contribution of Group V Phospholipase A2

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 25
Author(s):  
Masaya Koganesawa ◽  
Munehiro Yamaguchi ◽  
Sachin K. Samuchiwal ◽  
Barbara Balestrieri
Keyword(s):  
Phospholipase A2 ◽  
Mass Spectrometry Analysis ◽  
Prostaglandin D2 ◽  
Activated Macrophages ◽  
Bioactive Lipids ◽  
Group V ◽  
Spectrometry Analysis ◽  
Ifn Γ ◽  
Type 2 Inflammation

Macrophages activated by Interleukin (IL)-4 (M2) or LPS+ Interferon (IFN)γ (M1) perform specific functions respectively in type 2 inflammation and killing of pathogens. Group V phospholipase A2 (Pla2g5) is required for the development and functions of IL-4-activated macrophages and phagocytosis of pathogens. Pla2g5-generated bioactive lipids, including lysophospholipids (LysoPLs), fatty acids (FAs), and eicosanoids, have a role in many diseases. However, little is known about their production by differentially activated macrophages. We performed an unbiased mass-spectrometry analysis of phospholipids (PLs), LysoPLs, FAs, and eicosanoids produced by Wild Type (WT) and Pla2g5-null IL-4-activated bone marrow-derived macrophages (IL-4)BM-Macs (M2) and (LPS+IFNγ)BM-Macs (M1). Phosphatidylcholine (PC) was preferentially metabolized in (LPS+IFNγ)BM-Macs and Phosphatidylethanolamine (PE) in (IL-4)BM-Macs, with Pla2g5 contributing mostly to metabolization of selected PE molecules. While Pla2g5 produced palmitic acid (PA) in (LPS+IFNγ)BM-Macs, the absence of Pla2g5 increased myristic acid (MA) in (IL-4)BM-Macs. Among eicosanoids, Prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2) were significantly reduced in (IL-4)BM-Macs and (LPS+IFNγ)BM-Macs lacking Pla2g5. Instead, the IL-4-induced increase in 20-carboxy arachidonic acid (20CooH AA) was dependent on Pla2g5, as was the production of 12-hydroxy-heptadecatrienoic acid (12-HHTrE) in (LPS+IFNγ)BM-Macs. Thus, Pla2g5 contributes to PE metabolization, PGE2 and PGD2 production independently of the type of activation, while in (IL-4)BM-Macs, Pla2g5 regulates selective lipid pathways and likely novel functions.

scholarly journals Tuft cell-produced cysteinyl leukotrienes and IL-25 synergistically drive lung type 2 inflammation

2021 ◽  
Author(s):  
Saltanat Ualiyeva ◽  
Evan R Lemire ◽  
Amelia Boyd ◽  
Caitlin Wong ◽  
Juying Lai ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
Cysteinyl Leukotrienes ◽  
Tuft Cell ◽  
Tuft Cells ◽  
Lung Eosinophilia ◽  
Type 2 Inflammation

Aeroallergen sensing by airway epithelial cells can trigger pathogenic immune responses leading to chronic type 2 inflammation, the hallmark of airway diseases such as asthma. Airway tuft cells are specialized chemosensory epithelial cells and the dominant source of the epithelial cytokine IL-25 in the trachea and of cysteinyl leukotrienes (CysLTs) in the naive murine nasal mucosa. The interaction of IL-25 and CysLTs and the contribution of tuft cell-derived CysLTs to the development of allergen-triggered inflammation in the airways has not been clarified. Here we show that inhalation of LTC4 in combination with a subthreshold dose of IL25 leads to dramatic synergistic induction of type 2 inflammation throughout the lungs, causing rapid eosinophilia, dendritic cell (DC) and inflammatory type 2 innate lymphoid cell (ILC2) expansion, and goblet cell metaplasia. While lung eosinophilia is dominantly mediated through the classical CysLT receptor CysLT1R, type 2 cytokines and activation of innate immune cells require signaling through both CysLT1R and CysLT2R. Tuft cell-specific deletion of the terminal enzyme requisite for CysLT production, Ltc4s, was sufficient to reduce both the innate immune response in the lung: eosinophilia, ILC2 activation and DC recruitment, and the systemic immune response in the draining lymph nodes after inhalation of the mold aeroallergen Alternaria. Our findings identify surprisingly potent synergy of CysLTs and IL-25 downstream of aeroallergen-trigged activation of airway tuft cells leading to a highly polarized type 2 immune response and further implicate airway tuft cells as powerful modulators of type 2 immunity in the lungs.

Innate immunity alterations in Type 2 Diabetes Mellitus: understanding infection susceptibility

2020 ◽  
Vol 20 ◽  
Author(s):  
Ochoa-González Fátima de Lourdes ◽  
González-Curiel Irma Elizabeth ◽  
Cervantes-Villagrana Al-berto Rafael ◽  
Fernández-Ruiz Julio Cesar ◽  
Castañeda-Delgado Julio Enrique
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Immune Response ◽  
Type 2 Diabetes Mellitus ◽  
Innate Immune Response ◽  
Adult Population ◽  
International Diabetes Federation ◽  
Innate Immune ◽  
Cellular Mechanisms

: Diabetes is a chronic disease characterized by marked alterations in the metabolism of glucose andby high con-centrations of glucose in the blood due to a decreased insulin production or resistance to the action of this hormone in pe-ripheral tissues. The International Diabetes Federation estimates a global incidence of diabetes of about 10% in the adult population (20 -79 years old), some 430 million cases reported worldwide in 2018. It is well documented that people with diabetes have a higher susceptibility to infectious diseases and therefore show higher morbidity and mortality compared to the non-diabetic population. Given that the innate immune response plays a fundamental role in protecting against invading pathogens through a myriad of humoral and cellular mechanisms, the present work makes a comprehensive review of the innate immune alterations in patients with type 2 diabetes mellitus (T2D) as well as a brief description of the molecular events leading or associated to such conditions.We show that in these patients a compromised innate immune response in-creases susceptibility to infections.

scholarly journals Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation

2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Airway Diseases ◽  
Type 2 Cytokines ◽  
Lymphoid Organogenesis ◽  
Deficient Mice

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.

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