Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection.
Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific C...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-03-01
|
Series: | PLoS Pathogens |
Online Access: | https://doi.org/10.1371/journal.ppat.1004701 |
id |
doaj-6f3bf1d6300e41919e7d294bbe3969cf |
---|---|
record_format |
Article |
spelling |
doaj-6f3bf1d6300e41919e7d294bbe3969cf2021-04-21T17:47:18ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-03-01113e100470110.1371/journal.ppat.1004701Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection.Darin L WiesnerCharles A SpechtChrono K LeeKyle D SmithLiliane MukaremeraS Thera LeeChun G LeeJack A EliasJudith N NielsenDavid R BoulwarePaul R BohjanenMarc K JenkinsStuart M LevitzKirsten NielsenPulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection.https://doi.org/10.1371/journal.ppat.1004701 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Darin L Wiesner Charles A Specht Chrono K Lee Kyle D Smith Liliane Mukaremera S Thera Lee Chun G Lee Jack A Elias Judith N Nielsen David R Boulware Paul R Bohjanen Marc K Jenkins Stuart M Levitz Kirsten Nielsen |
spellingShingle |
Darin L Wiesner Charles A Specht Chrono K Lee Kyle D Smith Liliane Mukaremera S Thera Lee Chun G Lee Jack A Elias Judith N Nielsen David R Boulware Paul R Bohjanen Marc K Jenkins Stuart M Levitz Kirsten Nielsen Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. PLoS Pathogens |
author_facet |
Darin L Wiesner Charles A Specht Chrono K Lee Kyle D Smith Liliane Mukaremera S Thera Lee Chun G Lee Jack A Elias Judith N Nielsen David R Boulware Paul R Bohjanen Marc K Jenkins Stuart M Levitz Kirsten Nielsen |
author_sort |
Darin L Wiesner |
title |
Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. |
title_short |
Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. |
title_full |
Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. |
title_fullStr |
Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. |
title_full_unstemmed |
Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. |
title_sort |
chitin recognition via chitotriosidase promotes pathologic type-2 helper t cell responses to cryptococcal infection. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2015-03-01 |
description |
Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection. |
url |
https://doi.org/10.1371/journal.ppat.1004701 |
work_keys_str_mv |
AT darinlwiesner chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT charlesaspecht chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT chronoklee chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT kyledsmith chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT lilianemukaremera chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT stheralee chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT chunglee chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT jackaelias chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT judithnnielsen chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT davidrboulware chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT paulrbohjanen chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT marckjenkins chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT stuartmlevitz chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection AT kirstennielsen chitinrecognitionviachitotriosidasepromotespathologictype2helpertcellresponsestocryptococcalinfection |
_version_ |
1714665802662150144 |