TY  - JOUR
A1  - Baptista, Marisa A.P.
A1  - Keszei, Marton
A1  - Oliveira, Mariana
A1  - Sunahara, Karen K.S.
A1  - Andersson, John
A1  - Dahlberg, Carin I.M.
A1  - Worth, Austen J.
A1  - Liedén, Agne
A1  - Kuo, I-Chun
A1  - Wallin, Robert P.A.
A1  - Snapper, Scott B.
A1  - Eidsmo, Liv
A1  - Scheynius, Annika
A1  - Karlsson, Mikael C.I.
A1  - Bouma, Gerben
A1  - Burns, Siobhan O.
A1  - Forsell, Mattias N.E.
A1  - Thrasher, Adrian J.
A1  - Nylén, Susanne
A1  - Westerberg, Lisa S.
T1  - Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells
JF  - Nature Communications
N2  - Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in theWASp gene.
Decreased cellular responses in WASp-deficient cells have been interpreted to mean that
WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an
exception to this concept and show that WASp-deficient dendritic cells have increased
activation of Rac2 that support cross-presentation to CD8þ T cells. Using two different skin
pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin
and increased expansion of IFNg-producing CD8þ T cells in the draining lymph node and
spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8þ
T cells at the expense of CD4þ T cells. WASp-deficient dendritic cells induce increased
cross-presentation to CD8þ T cells by activating Rac2 that maintains a near neutral pH of
phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2
signalling pathways in dendritic cells.
KW  - Cell signalling
KW  - Dendritic cells
KW  - Disease genetics
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165966
VL  - 7
ER  - 
TY  - JOUR
A1  - Lutz, Manfred B.
A1  - Heuer, Marion
A1  - Behlich, Anna-Sophie
A1  - Lee, Ji-Sook
A1  - Ribechini, Eliana
A1  - Jo, Eun-Kyeong
T1  - The 30-kDa and 38-kDa antigens from Mycobacterium tuberculosis induce partial maturation of human dendritic cells shifting CD4+ T cell responses towards IL-4 production
JF  - BMC Immunology
N2  - Background

Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases. Although 99% of individuals infected with Mtb develop a CD4+ Th1 and CD8+ T cell mediated immunity as measured by tuberculin skin test, this results only in partial protection and Mtb vaccines are not effective. Deviation of immune responses by pathogens towards a Th2 profile is a common mechanism of immune evasion, typically leading to the persistence of the microbes.

Results

Here we tested the stimulatory capacity of selective Mtb antigens on human monocyte-derived dendritic cell (DC) maturation and cytokine production. DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers. All Mtb antigens induced variable levels of IL-6 and low levels of IL-10, there was no release of IL-12p70 detectable. Substantial IL-12p40 production was restricted to LPS or H37Ra and H37Rv preparations. Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4+ T cells after secondary stimulation as compared to H37Ra and H37Rv preparations.

Conclusion

Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.
KW  - Dendritic cells
KW  - Mycobacterium tuberculosis
KW  - T helper cell responses
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96871
UR  - http://www.biomedcentral.com/1471-2172/14/48
ER  -