Eosinophils are recruited in response to chitin exposure and enhance Th2-mediated immune pathology in aspergillus Fumigatus infection

Evan M. O'Dea, Nansalmaa Amarsaikhan, Hongtao Li, Joshua Downey, Emery Steele, Steven J. Van Dyken, Richard M. Locksley, Steven Templeton

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3199-3205
Number of pages7
JournalInfection and Immunity
Volume82
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Chitin
Aspergillus fumigatus
Eosinophils
Chemokine CCL11
Pathology
Lung
Fungal Spores
Eosinophilia
Infection
Morbidity
Chemokine CCL22
Host-Pathogen Interactions
Chitinases
Bronchoalveolar Lavage Fluid
Cellular Structures
Germination
Interleukin-4
Cell Wall
Interferon-gamma
Neutrophils

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Eosinophils are recruited in response to chitin exposure and enhance Th2-mediated immune pathology in aspergillus Fumigatus infection. / O'Dea, Evan M.; Amarsaikhan, Nansalmaa; Li, Hongtao; Downey, Joshua; Steele, Emery; Van Dyken, Steven J.; Locksley, Richard M.; Templeton, Steven.

In: Infection and Immunity, Vol. 82, No. 8, 2014, p. 3199-3205.

Research output: Contribution to journalArticle

O'Dea, Evan M. ; Amarsaikhan, Nansalmaa ; Li, Hongtao ; Downey, Joshua ; Steele, Emery ; Van Dyken, Steven J. ; Locksley, Richard M. ; Templeton, Steven. / Eosinophils are recruited in response to chitin exposure and enhance Th2-mediated immune pathology in aspergillus Fumigatus infection. In: Infection and Immunity. 2014 ; Vol. 82, No. 8. pp. 3199-3205.
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