Universität zu Köln

Perez-Nazario, Nelissa, Rangel-Moreno, Javier ORCID: 0000-0002-9738-1182, O'Reilly, Michael A., Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Gigliotti, Francis and Wright, Terry W. (2013). Selective Ablation of Lung Epithelial IKK2 Impairs Pulmonary Th17 Responses and Delays the Clearance of Pneumocystis. J. Immunol., 191 (9). S. 4720 - 4731. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 1550-6606

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Abstract

Pneumocystis is an atypical fungal pathogen that causes severe, often fatal pneumonia in immunocompromised patients. Healthy humans and animals also encounter this pathogen, but they generate a protective CD4(+) T cell-dependent immune response that clears the pathogen with little evidence of disease. Pneumocystis organisms attach tightly to respiratory epithelial cells, and in vitro studies have demonstrated that this interaction triggers NF-kappa B-dependent epithelial cell responses. However, the contribution of respiratory epithelial cells to the normal host response to Pneumocystis remains unknown. I kappa B kinase 2 (IKK2) is the upstream kinase that is critical for inducible NF-kappa B activation. To determine whether IKK2-dependent lung epithelial cell (LEC) responses contribute to the anti-Pneumocystis immune response in vivo, transgenic mice with LEC-specific deletion of IKK2 (IKK2(Delta LEC)) were generated. Compared to wild-type mice, IKK2(Delta LEC) mice exhibited a delayed onset of Th17 and B cell responses in the lung and delayed fungal clearance. Importantly, delayed Pneumocystis clearance in IKK2(Delta LEC) mice was associated with an exacerbated immune response, impaired pulmonary function, and altered lung histology. These data demonstrate that IKK2-dependent LEC responses are important regulators of pulmonary adaptive immune responses and are required for optimal host defense against Pneumocystis infection. LECs likely set the threshold for initiation of the pulmonary immune response and serve to prevent exacerbated lung inflammation by promoting the rapid control of respiratory fungal infection.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Perez-Nazario, Nelissa UNSPECIFIED UNSPECIFIED UNSPECIFIED Rangel-Moreno, Javier UNSPECIFIED orcid.org/0000-0002-9738-1182 UNSPECIFIED O'Reilly, Michael A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Gigliotti, Francis UNSPECIFIED UNSPECIFIED UNSPECIFIED Wright, Terry W. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-473007
DOI:	10.4049/jimmunol.1301679
Journal or Publication Title:	J. Immunol.
Volume:	191
Number:	9
Page Range:	S. 4720 - 4731
Date:	2013
Publisher:	AMER ASSOC IMMUNOLOGISTS
Place of Publication:	BETHESDA
ISSN:	1550-6606
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; CARINII-PNEUMONIA; HOST DEFENSES; CD4+ CELLS; T-CELLS; MICE; INFECTION; ACTIVATION; RESISTANCE; IMMUNE Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47300