To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Synergy between CD40 and … - University of Gothenburg, Sweden Till startsida
To content Read more about how we use cookies on

Synergy between CD40 and MyD88 does not influence host survival to Salmonella infection

Journal article
Authors Ulf Alexander Wenzel
Maria Fernández-Santoscoy
M. A. Tam
Pia Tegtmeyer
Mary Jo Wick
Published in Frontiers in Immunology
Volume 6
ISSN 1664-3224
Publication year 2015
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Language en
Keywords dendritic cell, Salmonella, NF kappa B, MyD88, CD40, t-cell responses, in-vivo requires, dendritic cells, immune-response, antigen presentation, activation, costimulation, ligation, monocyte, pathway, Immunology
Subject categories Immunology in the medical area


Previous studies using purified toll-like receptor (TLR) ligands plus agonistic anti-CD40 antibodies showed that TLRs and CD40 can act synergistically on dendritic cells (DCs) to optimize T cell activation and Th1 differentiation. However, a synergistic effect of TLRs and CD40 during bacterial infection is not known. Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues. In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-gamma and have elevated IL-10. A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where 01-11 T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA(323-339) peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs. By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-gamma that was lower than WT or CD40(-/-) DCs. DKO DCs pulsed with HKSOVA, but not with OVA or OVA(323-339), had increased IL-10 relative to MyD88(-/-) DCs. Finally, HKSHKSOVA-pulsed MyD88(-/-) and DKO DCs had similar and low induction of NF kappa B-dependent and independent genes upon co-culture with 01-11 cells. Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-gamma or IL-10. However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (01-11 proliferation and IFN-gamma production) DC functions and depend on the complexity of the antigen. Indeed, synergistic effects observed using purified ligands and well-defined antigens may not necessarily apply when complex antigens, such as live bacteria, challenge the immune system.

Page Manager: Webmaster|Last update: 9/11/2012

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?