Chronic hypersensitivity pneumonitis caused by <i>Saccharopolyspora rectivirgula</i> is not associated with a switch to a Th2 response

Andrews, Kelly; Ghosh, Manik C.; Schwingshackl, Andreas; Rapalo, Gabriel; Luellen, Charlean L.; Waters, Christopher M.; Fitzpatrick, Elizabeth

doi:10.1152/ajplung.00305.2015

Cited by 17 publications

(12 citation statements)

References 39 publications

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“…Experimental models of HP show that IL-17A is involved in lung inflammation induced by Saccharopolyspora rectivirgula (7)(8)(9)(10)(11), pigeon dropping extract (PDE) (12), and Stachybotrys chartarum (13). IL-17A is involved in a variety of immunological responses, such as enhanced production of proinflammatory cytokines and chemokines and direct immune cell recruitment (14,15).…”

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confidence: 99%

IL-17A–Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis

Yamana

Okamoto

Ishizuka

et al. 2021

The Journal of Immunology

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Hypersensitivity pneumonitis (HP) typically presents with interstitial inflammation and granulomas induced by an aberrant immune response to inhaled Ags in sensitized individuals. Although IL-17A is involved in the development of HP, the cellular sources of IL-17A and the mechanisms by which IL-17A contributes to granuloma formation remain unclear. Recent studies report that gd T cells produce IL-17A and exhibit memory properties in various diseases. Therefore, we focused on IL-17Asecreting memory gd T cells in the sensitization phase and aimed to elucidate the mechanisms by which IL-17A contributes to granuloma formation in HP. We induced a mouse model of HP using pigeon dropping extract (PDE) in wild-type and IL-17A knockout (IL-17A 2/2 ) mice. IL-17A 2/2 mice exhibited reduced granulomatous areas, attenuated aggregation of CD11b + alveolar macrophages, and reduced levels of CCL2, CCL4, and CCL5 in the bronchoalveolar lavage fluid. Among IL-17A + cells, more gd T cells than CD4 + cells were detected after intranasal PDE administration. Interestingly, the expansion of IL-17A-secreting Vg4 + or Vg1 2 Vg4 2 cells of convalescent mice was enhanced in response to the sensitizing Ag. Additionally, coculture of macrophages with PDE and Vg4 + cells purified from PDE-exposed convalescent mice produced significantly more IL-17A than coculture with Vg4 + cells from naive mice. Our findings demonstrate that in the sensitization phase of HP, IL-17A-secreting memory gd T cells play a pivotal role. Furthermore, we characterized the IL-17A/CCL2, CCL4, CCL5/CD11b + alveolar macrophage axis, which underlies granuloma formation in HP. These findings may lead to new clinical examinations or therapeutic targets for HP.

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confidence: 99%

IL-17A–Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis

Yamana

Okamoto

Ishizuka

et al. 2021

The Journal of Immunology

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“…In contrast to these findings in our healthy mold-exposed cohort of agricultural workers, we and others previously reported that patients with Aspergillus- associated hypersensitivity diseases, such as ABPA, display strongly elevated Th17 cytokine responses to A. fumigatus antigens [ 12 , 28 ]. Although important in the initial stage of fungal clearance [ 29 , 30 , 31 , 32 ], enhanced Th17-cell activation has been associated with Aspergillus airway colonization and fungal persistence and is considered a driving factor in the establishment of hypersensitivity pneumonitis, a potential complication of chronic occupational mold exposure [ 28 , 33 , 34 , 35 , 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic Occupational Mold Exposure Drives Expansion of Aspergillus-Reactive Type 1 and Type 2 T-Helper Cell Responses

Lauruschkat

Etter

Schnack

et al. 2021

JoF

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Occupational mold exposure can lead to Aspergillus-associated allergic diseases including asthma and hypersensitivity pneumonitis. Elevated IL-17 levels or disbalanced T-helper (Th) cell expansion were previously linked to Aspergillus-associated allergic diseases, whereas alterations to the Th cell repertoire in healthy occupationally exposed subjects are scarcely studied. Therefore, we employed functional immunoassays to compare Th cell responses to A. fumigatus antigens in organic farmers, a cohort frequently exposed to environmental molds, and non-occupationally exposed controls. Organic farmers harbored significantly higher A. fumigatus-specific Th-cell frequencies than controls, with comparable expansion of Th1- and Th2-cell frequencies but only slightly elevated Th17-cell frequencies. Accordingly, Aspergillus antigen-induced Th1 and Th2 cytokine levels were strongly elevated, whereas induction of IL-17A was minimal. Additionally, increased levels of some innate immune cell-derived cytokines were found in samples from organic farmers. Antigen-induced cytokine release combined with Aspergillus-specific Th-cell frequencies resulted in high classification accuracy between organic farmers and controls. Aspf22, CatB, and CipC elicited the strongest differences in Th1 and Th2 responses between the two cohorts, suggesting these antigens as potential candidates for future bio-effect monitoring approaches. Overall, we found that occupationally exposed agricultural workers display a largely balanced co-expansion of Th1 and Th2 immunity with only minor changes in Th17 responses.

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“…Moreover, fungi such as Aspergillus spp. have also been epidemiologically and serologically linked to HP and a more complex immune response that includes T H 2 cell activation in more severe and chronic forms of HP [51,52]. Notably, inclusion of fungi and viable organisms of any type in models of HP has been lacking thus far.…”

Section: Discussionmentioning

confidence: 99%

Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide

et al. 2021

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Background Inhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic mold Aspergillus niger (A. niger). Methods C57BL/6J mice were intranasally challenged with the viable spores of A. niger with and without 1 μg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined. Results In comparison to mice challenged only with A. niger, addition of LPS (1 μg) to A. niger abrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies. Conclusions In contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.

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Chronic hypersensitivity pneumonitis caused by Saccharopolyspora rectivirgula is not associated with a switch to a Th2 response

Abstract: Andrews K, Ghosh MC, Schwingshackl A, Rapalo G, Luellen C, Waters CM, Fitzpatrick EA. Chronic hypersensitivity pneumonitis caused by Saccharopolyspora rectivirgula is not associated with a switch to a Th2 response.

Cited by 17 publications

References 39 publications

IL-17A–Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis

IL-17A–Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis

Chronic Occupational Mold Exposure Drives Expansion of Aspergillus-Reactive Type 1 and Type 2 T-Helper Cell Responses

Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide

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