Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+ CD11c+ cells

Daito, Hisayoshi; Kikuchi, Toshiaki; Sakakibara, Tomohiro; Gomi, Katsushige; Damayanti, Triya; Zaini, Jamal; Tode, Naoki; Kanehira, Masafumi; Koyama, Shohei; Fujimura, Shigeru; Ebina, Masahito; Ishii, Ken J.; Akira, Shizuo; Takai, Toshiro; Watanabe, Akira; Nukiwa, Toshihiro

doi:10.1183/09031936.00177110

Cited by 16 publications

(11 citation statements)

References 52 publications

(64 reference statements)

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“…There is an ongoing discussion of whether HTL should be regarded as hypersensitivity pneumonitis, infection, both or a disease entity of its own [8]. Chest radiography usually, but not always, shows scattered interstitial infiltrates or nodules.…”

mentioning

confidence: 99%

Hot tub lung: an occupational hazard

Fjällbrant

Åkerström

Svensson

et al. 2013

European Respiratory Review

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mentioning

confidence: 99%

Hot tub lung: an occupational hazard

Fjällbrant

Åkerström

Svensson

et al. 2013

European Respiratory Review

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“…For example, we have shown previously that TLR9 is required for recruitment and activation of DC in murine models of Gram-negative bacterial pneumonia and SC-induced HP (46–48). Similarly, Daito and colleagues have recently identified the importance of TLR9-mediated DC responses in Mycobacterium avium -induced granulomatous inflammation (49). In the aforementioned study, TLR9 −/− mice failed to mount a Th1-skewed cytokine response and lung peribronchial, perivascular and parenchymal inflammation after exposure to a killed M. avium strain.…”

Section: Discussionmentioning

confidence: 96%

TLR9-Dependent IL-23/IL-17 Is Required for the Generation of Stachybotrys chartarum–Induced Hypersensitivity Pneumonitis

Bhan

Newstead

Zeng

et al. 2013

The Journal of Immunology

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Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that develops following repeated exposure to inhaled particulate antigen. Stachybotrys chartarum (SC) is a dimorphic fungus that has been implicated in a number of respiratory illnesses, including HP (1). In this study we have developed a murine model of SC- induced HP that reproduces pathology observed in human HP and hypothesized that TLR9–mediated IL-23/IL-17 responses are required for the generation of granulomatous inflammation induced by inhaled SC. Mice that undergo i.p. sensitization and i.t. challenge with 106 SC spores developed granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of T cells. SC sensitization and challenge resulted in robust pulmonary expression of IL-17 and IL-23. SC-mediated granulomatous inflammation required intact IL-23/IL-17 responses and required TLR9, as TLR9−/− mice displayed reduced IL-17 and IL-23 expression in whole lung associated with decreased accumulation of IL-17 expressing CD4+ and γδ T cells. As compared to SC-sensitized dendritic cells (DC) isolated from WT mice, DC isolated from TLR9−/− mice had a reduced ability to produce IL-23 in responses to SC. Moreover, shRNA knockdown of IL-23 in DC abolished IL-17 production from splenocytes in response to antigen challenge. Finally, the i.t. reconstitution of IL-23 in TLR9−/− mice recapitulated the immunopathology observed in WT mice. In conclusion, our studies suggest that TLR9 is critical for development of Th17-mediated granulomatous inflammation in the lung in response to SC.

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“…and a cross referencing of article references, returned 70 cases in the English literature. 1,2,8,[11][12][13][14][15][16] The articles mostly describe healthy middle aged individuals, with the mean age of 58.8 years (range 30 to 69). No sex predilection was noted (Males 51% and females 49%).…”

Section: Discussionmentioning

confidence: 99%