Eosinophils Are Recruited in Response to Chitin Exposure and Enhance Th2-Mediated Immune Pathology in Aspergillus fumigatus Infection

Abstract

In patients infected with the fungus Aspergillus fumigatus, Th1 responses are considered protective, while Th2 responses are associated with increased morbidity and mortality. How host-pathogen interactions influence the development of these protective or detrimental immune responses is not clear. We compared lung immune responses to conidia from two fungal isolates that expressed different levels of the fungal cell wall component chitin. We observed that repeated aspirations of the high-chitinexpressing isolate Af5517 induced increased airway eosinophilia in the lungs of recipient mice compared to the level of eosinophilia induced by isolate Af293. CD4؉ T cells in the bronchoalveolar lavage fluid (BALF) of Af5517-aspirated mice displayed decreased gamma interferon secretion and increased interleukin-4 transcription. In addition, repeated aspirations of Af5517 induced lung transcription of the Th2-associated chemokines CCL11 (eotaxin-1) and CCL22 (macrophage-derived chemokine). Eosinophil recruitment in response to conidial aspiration was correlated with the level of chitin exposure during germination and was decreased by constitutive lung chitinase expression. Moreover, eosinophil-deficient mice subjected to multiple aspirations of Af5517 prior to neutrophil depletion and infection exhibited decreased morbidity and fungal burden compared to the levels of morbidity and fungal burden found in wild-type mice. These results suggest that exposure of chitin in germinating conidia promotes eosinophil recruitment and ultimately induces Th2-skewed immune responses after repeated aspiration. Furthermore, our results suggest that eosinophils should be examined as a potential therapeutic target in patients that mount poorly protective Th2 responses to A. fumigatus infection.

Immunity against fungi

“…Consistent with these findings, chitosan-deficient (i.e., deacetylated chitin) cryptococcal strains elicit cytokine mediators that promote a Th1-biased response (132). Similarly, the chitin content of individual A. fumigatus strains correlates with the magnitude of Th2 responses and lung eosinophil recruitment (133). The role of eosinophils in fungal clearance remains poorly understood, with several recent reports suggesting these cells help mediate fungal clearance (134)(135)(136).…”

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

“…In fact, most of these patients didn't have asthma according to their clinical records. Thus, the fungal infection might be a potential cause to recruit eosinophils infiltration into airways (30), because Aspergillus species infection was found to be the most common pathogen in these excised lung tissue sections from patients with non-CF bronchiectasis.…”

Küf Mantari Allerji̇si̇ Ve İmmünoterapi̇

“…Mold'ların immün sistem üzerine değişik etkilerine ilaveten, Th1 yolağının reaktivitesini azaltmaları yanında Th2 yolağınınkini artırırlar. Alternaria alternata serin proteazı'nın proteazla aktive olan reseptör-2 (PAR-2) üzerinden havayolu epitel hücresi, Dendritik hücre gibi doğal bağışıklık hücrelerini uyararak Th2 yolağı üzerinden allerjik akciğer enflamasyonuna yol açtığı bilinmektedir (10,13,14).…”