Chitinase 3-like-1 protects airway function despite promoting type 2 inflammation during fungal-associated allergic airway inflammation

2021 ◽  
Author(s):  
Joseph J. Mackel ◽  
Jaleesa M. Garth ◽  
MaryJane Jones ◽  
Diandra A. Ellis ◽  
Jonathan P. Blackburn ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Periodic Acid ◽  
Acute Infection ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Allergic Airway Inflammation ◽  
Lung Edema ◽  
Periodic Acid Schiff ◽  
Wide Range ◽  
Type 2 Inflammation

Exposure to fungi can result in a wide range of comorbidities depending on the immune status of the host. Chronic exposure and reactivity to fungi such as Aspergillus fumigatus can result in conditions such as severe asthma with fungal sensitization (SAFS) or allergic bronchopulmonary aspergillosis (ABPA). However, the pathophysiology of SAFS and ABPA are not well understood. Here, we report that the chitinase-like protein YKL-40 is elevated in lung lavage fluid from human asthmatics that are sensitized to fungi. Initial studies demonstrated that mice deficient in the murine ortholog of YKL-40, breast regression protein-39 (BRP-39, chitinase-3-like 1, Chi3l1), were not more susceptible to acute infection with A. fumigatus. However, in an experimental model of fungal-associated allergic airway inflammation (fungal asthma), Chi3l1-/- mice had significantly increased airway hyperresponsiveness (AHR). Surprisingly, increased AHR in Chi3l1-/- mice occurred in the presence of significantly lower type 2 responses (decreased eosinophil numbers and decreased IL-4, IL-5, IL-33, CCL17 and CCL22 levels), although type 1 and type 17 responses were not different. Increased AHR was not associated with differences in Periodic-acid-Schiff staining of lung tissue, differences in the expression of Muc5ac and Clca3, nor differences in lung edema. Bone marrow chimera studies revealed that the presence of BRP-39 in either the hematopoietic or non-hematopoietic compartment was sufficient for controlling AHR during fungal asthma. Collectively, these results indicate that BRP-39 protects against AHR during fungal asthma despite contributing to type 2 inflammation, thus highlighting an unexpected protective role for BRP-39 in allergic fungal asthma.

scholarly journals An anti-inflammatory eicosanoid switch mediates the suppression of type-2 inflammation by helminth larval products

2020 ◽  
Vol 12 (540) ◽  
pp. eaay0605 ◽  
Author(s):  
Marta de los Reyes Jiménez ◽  
Antonie Lechner ◽  
Francesca Alessandrini ◽  
Sina Bohnacker ◽  
Sonja Schindela ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Mitogen Activated Protein Kinase ◽  
Metabolic Enzyme ◽  
Prostaglandin E ◽  
Lipoxygenase Pathway ◽  
Anti Inflammatory ◽  
Type 2 Inflammation ◽  
Allergy And Asthma

Eicosanoids are key mediators of type-2 inflammation, e.g., in allergy and asthma. Helminth products have been suggested as remedies against inflammatory diseases, but their effects on eicosanoids are unknown. Here, we show that larval products of the helminth Heligmosomoides polygyrus bakeri (HpbE), known to modulate type-2 responses, trigger a broad anti-inflammatory eicosanoid shift by suppressing the 5-lipoxygenase pathway, but inducing the cyclooxygenase (COX) pathway. In human macrophages and granulocytes, the HpbE-driven induction of the COX pathway resulted in the production of anti-inflammatory mediators [e.g., prostaglandin E2 (PGE2) and IL-10] and suppressed chemotaxis. HpbE also abrogated the chemotaxis of granulocytes from patients suffering from aspirin-exacerbated respiratory disease (AERD), a severe type-2 inflammatory condition. Intranasal treatment with HpbE extract attenuated allergic airway inflammation in mice, and intranasal transfer of HpbE-conditioned macrophages led to reduced airway eosinophilia in a COX/PGE2-dependent fashion. The induction of regulatory mediators in macrophages depended on p38 mitogen-activated protein kinase (MAPK), hypoxia-inducible factor-1α (HIF-1α), and Hpb glutamate dehydrogenase (GDH), which we identify as a major immunoregulatory protein in HpbE. Hpb GDH activity was required for anti-inflammatory effects of HpbE in macrophages, and local administration of recombinant Hpb GDH to the airways abrogated allergic airway inflammation in mice. Thus, a metabolic enzyme present in helminth larvae can suppress type-2 inflammation by inducing an anti-inflammatory eicosanoid switch, which has important implications for the therapy of allergy and asthma.

Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. airway hyperresponsiveness

2015 ◽  
Vol 309 (8) ◽  
pp. L789-L800 ◽  
Author(s):  
Akihiko Taniguchi ◽  
Nobuaki Miyahara ◽  
Koichi Waseda ◽  
Etsuko Kurimoto ◽  
Utako Fujii ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Allergic Airway Inflammation ◽  
T Helper ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Group 2 ◽  
Airway Responses

The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE−/−) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE−/− mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE+/+ mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE−/− mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

scholarly journals IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation

2018 ◽  
Vol 49 (1) ◽  
pp. 66-78 ◽  
Author(s):  
Diana C. Yánez ◽  
Hemant Sahni ◽  
Susan Ross ◽  
Anisha Solanki ◽  
Ching-In Lau ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

scholarly journals The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Morris Nechama ◽  
Jeahoo Kwon ◽  
Shuo Wei ◽  
Adrian Tun Kyi ◽  
Robert S. Welner ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Type 2 Immunity

scholarly journals Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin-induced allergic airway inflammation

Immunology ◽  
2014 ◽  
Vol 142 (2) ◽  
pp. 202-215 ◽  
Author(s):  
Wenwei Zhong ◽  
Wen Su ◽  
Yanjie Zhang ◽  
Qi Liu ◽  
Jinhong Wu ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
T Helper ◽  
Type 2 Immunity ◽  
Helper Type

Targeting SIRP-α protects from type 2-driven allergic airway inflammation

2010 ◽  
Vol 40 (12) ◽  
pp. 3510-3518 ◽  
Author(s):  
Marianne Raymond ◽  
Vu Quang Van ◽  
Manuel Rubio ◽  
Karl Welzenbach ◽  
Marika Sarfati
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation

scholarly journals Airway epithelial TSLP production of TLR2 drives type 2 immunity in allergic airway inflammation

2018 ◽  
Vol 48 (11) ◽  
pp. 1838-1850 ◽  
Author(s):  
Jiajia Lv ◽  
Qianying Yu ◽  
Jie Lv ◽  
Caixia Di ◽  
Xiaoliang Lin ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Airway Epithelial ◽  
Type 2 Immunity

scholarly journals AscarisLarval Infection and Lung Invasion Directly Induce Severe Allergic Airway Disease in Mice

2018 ◽  
Vol 86 (12) ◽  
Author(s):  
Jill E. Weatherhead ◽  
Paul Porter ◽  
Amy Coffey ◽  
Dana Haydel ◽  
Leroy Versteeg ◽  
...  
Keyword(s):  
Airway Remodeling ◽  
Periodic Acid ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Interleukin 4 ◽  
Lung Pathology ◽  
Periodic Acid Schiff ◽  
Content Type ◽  
Larval Migration

ABSTRACTAscaris lumbricoides(roundworm) is the most common helminth infection globally and a cause of lifelong morbidity that may include allergic airway disease, an asthma phenotype. We hypothesize thatAscarislarval migration through the lungs leads to persistent airway hyperresponsiveness (AHR) and type 2 inflammatory lung pathology despite resolution of infection that resembles allergic airway disease. Mice were infected withAscarisby oral gavage. Lung AHR was measured by plethysmography and histopathology with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stains, and cytokine concentrations were measured by using Luminex Magpix.Ascaris-infected mice were compared to controls or mice with allergic airway disease induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA).Ascaris-infected mice developed profound AHR starting at day 8 postinfection (p.i.), peaking at day 12 p.i. and persisting through day 21 p.i., despite resolution of infection, which was significantly increased compared to controls and OVA/OVA mice.Ascaris-infected mice had a robust type 2 cytokine response in both the bronchoalveolar lavage (BAL) fluid and lung tissue, similar to that of the OVA/OVA mice, including interleukin-4 (IL-4) (P < 0.01 andP< 0.01, respectively), IL-5 (P < 0.001 andP < 0.001), and IL-13 (P < 0.001 andP < 0.01), compared to controls. By histopathology,Ascaris-infected mice demonstrated early airway remodeling similar to, but more profound than, that in OVA/OVA mice. We found thatAscarislarval migration causes significant pulmonary damage, including AHR and type 2 inflammatory lung pathology that resembles an extreme form of allergic airway disease. Our findings indicate that ascariasis may be an important cause of allergic airway disease in regions of endemicity.

scholarly journals Dendritic Cells: Critical Regulators of Allergic Asthma

2020 ◽  
Vol 21 (21) ◽  
pp. 7930 ◽  
Author(s):  
Ioannis Morianos ◽  
Maria Semitekolou
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Allergic Airway Inflammation ◽  
Chronic Inflammatory Disease ◽  
Antigen Presenting ◽  
Airborne Allergens

Allergic asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness (AHR), chronic airway inflammation, and excessive T helper (Th) type 2 immune responses against harmless airborne allergens. Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system that act as a bridge between innate and adaptive immunity. Pertinent to allergic asthma, distinct DC subsets are known to play a central role in initiating and maintaining allergen driven Th2 immune responses in the airways. Nevertheless, seminal studies have demonstrated that DCs can also restrain excessive asthmatic responses and thus contribute to the resolution of allergic airway inflammation and the maintenance of pulmonary tolerance. Notably, the transfer of tolerogenic DCs in vivo suppresses Th2 allergic responses and protects or even reverses established allergic airway inflammation. Thus, the identification of novel DC subsets that possess immunoregulatory properties and can efficiently control aberrant asthmatic responses is critical for the re-establishment of tolerance and the amelioration of the asthmatic disease phenotype.

The Identification of Thyrotrophin-secreting Cells in the Pituitary Gland of the Minnow (Phoxinus phoxinus)

1955 ◽  
Vol s3-96 (34) ◽  
pp. 193-201
Author(s):  
E. J. W. BARRINGTON ◽  
A. J. MATTY
Keyword(s):  
Pituitary Gland ◽  
Positive Response ◽  
Periodic Acid ◽  
Periodic Acid Schiff ◽  
Phoxinus Phoxinus ◽  
Aldehyde Fuchsin ◽  
Median Zone ◽  
Cytological Characteristics

Evidence is given for the existence of two main types of cyanophil cell in the median zone of the glandular lobe (adenohypophysis) of the minnow, distinguishable by their distribution and by their cytological characteristics. Both types are positive to the periodic acid Schiff (PAS) technique, but one (type 2 of this account) also gives a positive response to the aldehyde-fuchsin (AF) technique of Gomori, as used by Halmi and by Purves and Griesbach in studies of the mammalian pituitary. In fish which have been immersed in thiouracil solution the type 2 cells show degranulation and vacuolation, and their characteristic positive AF response is very greatly weakened or lost. For these reasons the type 2 cells are believed to be responsible for the secretion of thyrotrophin, and appear to be very closely comparable with the thyrotroph cells of the pituitary of the rat.

Sign in / Sign up

Export Citation Format

Share Document