TY  - JOUR
A1  - Ribechini, Eliana
A1  - Eckert, Ina
A1  - Beilhack, Andreas
A1  - Du Plessis, Nelita
A1  - Walzl, Gerhard
A1  - Schleicher, Ulrike
A1  - Ritter, Uwe
A1  - Lutz, Manfred B.
T1  - Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell–killing capability
JF  - JCI Insight
N2  - Tuberculosis patients and mice infected with live Mycobacterium tuberculosis accumulate high numbers of myeloid-derived suppressor cells (MDSCs). Here, we hypothesized that dead M. tuberculosis vaccines also may induce MDSCs that could impair the efficacy of vaccination. We found that repeated injections of M. tuberculosis vaccines (heat-killed M. tuberculosis in incomplete Freund’s adjuvant, such as Montanide) but not single or control vaccines without M. tuberculosis strongly expanded CD11b\(^+\) myeloid cells in the spleen, leading to T cell suppression of proliferation and killing ex vivo. Dead M. tuberculosis vaccination induced the generation of CD11b\(^+\)Ly6C\(^{hi}\)CD115\(^+\) iNOS/Nos2\(^+\) monocytic MDSCs (M-MDSCs) upon application of inflammatory or microbial activation signals. In vivo these M-MDSCs were positioned strategically in the splenic bridging channels and then positioned in the white pulp areas. Notably, within 6–24 hours, in a Nos2-dependent fashion, they produced NO to rapidly kill conventional and plasmacytoid DCs while, surprisingly, sparing T cells in vivo. Thus, we demonstrate that M. tuberculosis vaccine induced M-MDSCs do not directly suppress effector T cells in vivo but, instead, indirectly by killing DCs. Collectively, we demonstrate that M. tuberculosis booster vaccines induce M-MDSCs in the spleen that can be activated to kill DCs. Our data suggest that formation of MDSCs by M. tuberculosis vaccines should be investigated also in clinical trials.
KW  - Immunology
KW  - Infectious disease
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201973
VL  - 13
IS  - 4
ER  - 
TY  - JOUR
A1  - Wieching, Anna
A1  - Benser, Jasmin
A1  - Kohlhauser-Vollmuth, Christina
A1  - Weisbrich, Bendikt
A1  - Streng, Andrea
A1  - Liese, Johannes G.
T1  - Clinical characteristics of pediatric hospitalizations associated with 2009 pandemic influenza a (H1N1) in Northern Bavaria, Germany
N2  - Background: The 2009 pandemic influenza A (H1N1) (PIA) virus infected large parts of the pediatric population with a wide clinical spectrum and an initially unknown complication rate. The aims of our study were to define clinical characteristics and outcome of pandemic influenza A (H1N1) 2009-associated hospitalizations (PIAH) in children <18 years of age. All hospitalized cases of children <18 years of age with laboratory-confirmed pandemic influenza A (H1N1) 2009 in the region of Wuerzburg (Northern Bavaria, Germany) between July 2009 and March 2010 were identified. For these children a medical chart review was performed to determine their clinical characteristics and complications. Results: Between July 2009 and March 2010, 94 PIAH (62% males) occurred in children <18 years of age, with a median age of 7 years (IQR: 3–12 years). Underlying diseases and predisposing factors were documented in 40 (43%) children; obesity (n = 12, 30%), asthma (n = 10, 25%) and neurologic disorders (n = 8, 20%) were most frequently reported. Sixteen (17%) children received oxygen supplementation; three (3%) children required mechanical ventilation. Six (6%) children were admitted to an intensive care unit, four of them with underlying chronic diseases. Conclusions: Most PIAH demonstrated a benign course of disease. However, six children (6%) needed treatment at an intensive care unit for severe complications.
KW  - Medizin
KW  - Influenza
KW  - Pediatric
KW  - Infectious disease
KW  - Hospitalization
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75657
ER  -