scholarly journals High Levels of Susceptibility and T Helper 2 Response in MyD88-Deficient Mice Infected with Leishmania major Are Interleukin-4 Dependent

2003 ◽  
Vol 71 (12) ◽  
pp. 7215-7218 ◽  
Author(s):  
Andrea Debus ◽  
Joachim Gläsner ◽  
Martin Röllinghoff ◽  
André Gessner

ABSTRACT Myeloid differentiation protein 88 (MyD88) is a general adaptor for the signaling cascade through receptors of the Toll/IL-1R family. When infected with Leishmania major parasites, MyD88-deficient mice displayed a dramatically enhanced parasite burden in their tissues similar to that found in susceptible BALB/c mice. In contrast, MyD88 knockout mice did not develop ulcerating lesions despite a lack of interleukin-12 (IL-12) production and a predominant T helper 2 cell response. Blockade of IL-4 produced early (day 1) after infection restored a protective T helper 1 response in MyD88 knockout mice.

Immunology ◽  
2000 ◽  
Vol 99 (1) ◽  
pp. 109-112 ◽  
Author(s):  
K. M. Gillespie ◽  
C.-C. Szeto ◽  
V. M. Betin ◽  
P. W. Mathieson

1998 ◽  
Vol 66 (8) ◽  
pp. 3968-3970 ◽  
Author(s):  
Magdalena Huber ◽  
Emma Timms ◽  
Tak W. Mak ◽  
Martin Röllinghoff ◽  
Michael Lohoff

ABSTRACT The results of earlier investigations that tested whether CD8+ T cells are required in the defense againstLeishmania major have been inconsistent. We used CD8-deficient mice to directly address this issue. After primary infection with L. major, CD8-deficient mice controlled the infection for over 1 year and mounted strong T helper 1 cell responses. Thus, CD8+ T cells are not required for the long-term control of a primary infection with L. major.


Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2668-2671 ◽  
Author(s):  
Raffaella Bonecchi ◽  
Silvano Sozzani ◽  
Johnny T. Stine ◽  
Walter Luini ◽  
Giovanna D’Amico ◽  
...  

Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The present study was designed to investigate the effect of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), on the production of MDC by human monocytes. IL-4 and IL-13 caused a time-dependent (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL, respectively) increase of MDC mRNA levels in monocytes. Increased expression of MDC mRNA was associated with protein release in the supernatant. MDC expression and production induced by IL-4 and IL-13 were inhibited by IFN-γ. IFN-γ also suppressed the constitutive expression of MDC in mature macrophages and dendritic cells. These results delineate an amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-γ and on the selectivity of this chemokine for polarized Th2 cells. © 1998 by The American Society of Hematology.


2008 ◽  
Vol 76 (6) ◽  
pp. 2448-2455 ◽  
Author(s):  
Angela M. Arenas-Gamboa ◽  
Thomas A. Ficht ◽  
Melissa M. Kahl-McDonagh ◽  
Allison C. Rice-Ficht

ABSTRACT The development of safe and efficacious immunization systems to prevent brucellosis is needed to overcome the disadvantages of the currently licensed vaccine strains that restrict their use in humans. Alginate microspheres coated with a protein of the parasite Fasciola hepatica (vitelline protein B [VpB]) and containing live Brucella melitensis attenuated mutant vjbR::Tn5 (BMEII1116) were evaluated for vaccine efficacy and immunogenicity in mice. A single immunization dose in BALB/c mice with the encapsulated vjbR mutant improved protection against wild-type B. melitensis 16M challenge compared to the nonencapsulated vaccine strain (P < 0.05). The encapsulated mutant was also shown to induce a sustained elevation of Immunoglobulin G levels. Cytokine secretion from spleen cells of mice vaccinated with the encapsulated vjbR::Tn5 revealed elevated secretion of gamma interferon and interleukin-12, but no interleukin-4, suggesting an induction of a T helper 1 response reflecting the enhanced immunity associated with microencapsulation. Together, these results suggest that microencapsulation of live attenuated organisms offers the ability to increase the efficacy of vaccine candidates.


Immunology ◽  
2003 ◽  
Vol 108 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Kevin G. J. Pollock ◽  
Margaret Conacher ◽  
Xiao-Qing Wei ◽  
James Alexander ◽  
James M. Brewer

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2668-2671 ◽  
Author(s):  
Raffaella Bonecchi ◽  
Silvano Sozzani ◽  
Johnny T. Stine ◽  
Walter Luini ◽  
Giovanna D’Amico ◽  
...  

Abstract Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The present study was designed to investigate the effect of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), on the production of MDC by human monocytes. IL-4 and IL-13 caused a time-dependent (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL, respectively) increase of MDC mRNA levels in monocytes. Increased expression of MDC mRNA was associated with protein release in the supernatant. MDC expression and production induced by IL-4 and IL-13 were inhibited by IFN-γ. IFN-γ also suppressed the constitutive expression of MDC in mature macrophages and dendritic cells. These results delineate an amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-γ and on the selectivity of this chemokine for polarized Th2 cells. © 1998 by The American Society of Hematology.


2004 ◽  
Vol 72 (8) ◽  
pp. 4924-4928 ◽  
Author(s):  
Uta G. Lange ◽  
Pietro Mastroeni ◽  
Jenefer M. Blackwell ◽  
Carmel B. Stober

ABSTRACT Successful resolution of infections by intracellular pathogens requires gamma interferon (IFN-γ). DNA vaccines promote T helper 1 (Th1) responses by triggering interleukin-12 (IL-12) release by dendritic cells (DC) through Toll-like receptor 9 (TLR9). In humans TLR9 is restricted to plasmacytoid DC. Here we show that DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination, which provides alternative ligands to bind TLR4 on myeloid DC, strongly biases towards Th1 responses compared to vaccination with DNA alone. This results in higher immunoglobulin G2a (IgG2a) responses compared to IgG1 responses, higher IFN-γ responses compared to IL-10 CD4+-T-cell responses, and enhanced protection against Leishmania major infection in susceptible BALB/c mice.


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