Immune defense mechanisms against Legionella longbeachae
Immune defense mechanisms against Legionella longbeachae
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dc.contributor.advisor | Garbi, Natalio | |
dc.contributor.author | Scheiding, Victoria Madeleine | |
dc.date.accessioned | 2020-04-27T20:32:13Z | |
dc.date.available | 2020-04-27T20:32:13Z | |
dc.date.issued | 30.01.2020 | |
dc.identifier.uri | https://hdl.handle.net/20.500.11811/8327 | |
dc.description.abstract | The pulmonary epithelial barrier is the first line of defense against pathogens invading the lungs. If those are able to overcome this first barrier, myeloid cells of the innate immune system are instrumental for the antimicrobial defense and can directly eliminate invading microorganisms. This work aimed to identify novel mechanisms by which pulmonary epithelial cells and myeloid cells eliminate invading bacteria from the lungs. For this, infections with Legionella longbeachae were used to investigate a severe and often fatal form of pneumonia in humans known as Legionnaires’ disease in a mouse model. Following infection, infiltration of immune cells was dominated by neutrophils and, to a lesser extent, by monocytes. In addition to this, a significantly higher fraction of neutrophils contained L. longbeachae bacteria compared with other myeloid immune cells. Within host cells, bacteria translocated effector proteins mostly into neutrophils, and were residing in a vacuole resembling the Legionella-containing vacuole, as known from infections with L. pneumophila. However, neutrophils played an important role in the in vivo clearance of L. longbeachae, as mice depleted of this cell type exhibited significantly higher bacterial burden in the lungs. Besides neutrophils, monocytes also contributed to the control of pulmonary L. longbeachae infections, while lymphoid immune cells had no effect on the clearance of the bacteria. Molecularly, it is well known that IL18 is important in anti-bacterial defense by inducing lymphocytes to release IFNγ. However, IL18 receptor (IL18R) expression on lymphoid cells did apparently not promote L. longbeachae clearance. Instead, expression by pulmonary stromal cells was required and sufficient for elimination of the bacteria. Stromal expression of the IL18 receptor was almost confined to the ciliated epithelial cell compartment in the bronchioles. IL18R signaling in those cells did not promote mucus production but it rather enhanced the anti-bactericidal activity of neutrophils. Therefore, these results indicate a non-canonical role of IL18 in the defense against pulmonary L. longbeachae infection, linking non-immune pulmonary epithelial cells with inflammatory neutrophils. | |
dc.language.iso | eng | |
dc.rights | In Copyright | |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | Legionella | |
dc.subject | Legionnaires' disease | |
dc.subject | Legionella longbeachae | |
dc.subject | Interleukin-18 | |
dc.subject | Interleukin-18-Rezeptor | |
dc.subject | Neutrophile | |
dc.subject | Epithelzellen | |
dc.subject | Lunge | |
dc.subject | Interleukin-18 receptor | |
dc.subject | neutrophils | |
dc.subject | epithel cells | |
dc.subject | lung | |
dc.subject.ddc | 500 Naturwissenschaften | |
dc.subject.ddc | 570 Biowissenschaften, Biologie | |
dc.subject.ddc | 610 Medizin, Gesundheit | |
dc.title | Immune defense mechanisms against Legionella longbeachae | |
dc.type | Dissertation oder Habilitation | |
dc.publisher.name | Universitäts- und Landesbibliothek Bonn | |
dc.publisher.location | Bonn | |
dc.rights.accessRights | openAccess | |
dc.identifier.urn | https://nbn-resolving.org/urn:nbn:de:hbz:5-57366 | |
ulbbn.pubtype | Erstveröffentlichung | |
ulbbnediss.affiliation.name | Rheinische Friedrich-Wilhelms-Universität Bonn | |
ulbbnediss.affiliation.location | Bonn | |
ulbbnediss.affiliation.otherLocation1 | Melbourne | |
ulbbnediss.affiliation.otherName1 | University of Melbourne | |
ulbbnediss.thesis.level | Dissertation | |
ulbbnediss.dissID | 5736 | |
ulbbnediss.date.accepted | 17.01.2020 | |
ulbbnediss.institute | Medizinische Fakultät / Institute : Institut für Experimentelle Immunologie (IEI) | |
ulbbnediss.fakultaet | Medizinische Fakultät | |
dc.contributor.coReferee | van Driel, Ian | |
ulbbnediss.contributor.orcid | https://orcid.org/0000-0002-0973-6909 |
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