CD40 and the immune response to parasitic infections

Subauste, Carlos S.

doi:10.1016/j.smim.2009.06.003

Cited by 20 publications

(21 citation statements)

References 148 publications

(176 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous animal studies have indicated the importance of the CD40-CD40L signaling pathway for protection against a variety of parasites (reviewed in [13]). CD40 stimulation induces anti-microbial activity against T. cruzi, mediated by the production of nitric oxide (NO) and of free radicals, which require IL-12 and IFN-γ production.…”

Section: Discussionmentioning

confidence: 99%

“…The interaction of CD40 and CD40L is important for activating antigen presenting cells, T cells and macrophages [12]. CD40-CD40L signaling has an important role during various parasite infections (reviewed in [13]). While strong CD40-CD40L signaling induces IL-12 and IFN-γ production and drives T cells to a Th1 phenotype, weak signaling induces IL-10 and TGF-β, allowing T cells to differentiate to a Th2 or T regulatory phenotype (reviewed in [14]).…”

Section: Introductionmentioning

confidence: 99%

“…CD40-CD40L signaling is also important for antibody isotype switching, and germinal center formation, and patients with congenital X-linked hyper IgM syndrome (X-HIM), caused by the lack of functional CD40L, present an increased incidence of infections with opportunistic pathogens (reviewed in [13]). Peripheral blood mononuclear cells (PBMC) from X-HIM patients also secrete markedly lower amounts of IFN-γ and IL-12 in response to T. gondii [16].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis

et al. 2013

View full text Add to dashboard Cite

BackgroundSoluble CD40 ligand (sCD40L) and matrix metalloproteinase 9 (MMP-9) are inflammation markers and have been poorly described in infectious disease. In this prospective study, we describe the sera kinetics of these two molecules in the course of treatment follow up in human visceral leishmaniasis (VL).MethodsSera from VL patients were collected before and during follow up of regular Antimony treatment. sCD40L and MMP-9 were measured by Luminex assay. Paired analysis by Wilcoxon signed test was used for comparison of values of the same subjects before and after initiation of treatment. Correlations between clinical data and parasite load with the serum levels of sCD40L and MMP-9 were performed by Spearman test. Tests were considered statistically significant if the probability of a type I error was less than 5% (p-value < 0.05).ResultsWhile sCD40L and MMP-9 were not observed in sera from non endemic controls which are at low risk of Leishmania chagasi infection, elevated levels were observed in sera from VL patients, and an increase in sCD40L and MMP-9 levels were detectable during the follow-up of VL patients undergoing antimony treatment. sCD40L levels were also high in individuals living in endemic settings at high risk of infection (endemic controls). Additionally, negative correlations were found between spleen sizes and MMP-9 before treatment and sCD40L at day 15 of treatment. Negative correlations were also found between parasite load with both sCD40L and MMP-9.ConclusionSerum sCD40L and MMP-9 are identified as new and simple biomarkers in two situations: (i) monitoring the success of therapy and (ii) predicting favorable clinical outcome of human VL.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Ninety-five percent of sCD40L fraction is released by activated platelets [13] and its interaction with the CD40 receptor plays an important role in the induction of efficient humoral and cellular immune responses. The co-stimulatory molecules, including CD40L, are capable of regulating inflammation, and their blood levels as well as their soluble isoforms may serve as markers of activity in diverse pathological conditions, including sepsis [37], tuberculosis [38], and parasitic diseases [39], among others. Patients with CF have an intense systemic inflammation in which platelets are involved.…”

Section: Discussionmentioning

confidence: 99%

A High Level of Soluble CD40L Is Associated with P. aeruginosa Infection in Patients with Cystic Fibrosis

et al. 2016

View full text Add to dashboard Cite

ObjectiveThe aim of this study was to evaluate whether the concentration of sCD40L, a product of platelet activation, correlates with the presence of Pseudomonas aeruginosa in the airway of patients with cystic fibrosis (CF) and to determine its possible clinical association.MethodsSixty patients with CF, ranging in age from 2 months to 36 years, were studied. The demographics, cystic fibrosis transmembrane conductance regulator (CFTR) genotype, spirometry measurements, radiographic and tomographic scans, platelet count in peripheral blood, sCD40L, IL-6, TNF-α and ICAM1 data were collected. Infection-colonization of the airway was evaluated using sputum and throat swab cultures; the levels of anti-Pseudomonas aeruginosa antibodies (Anti-PaAb) were evaluated.ResultsPatients with CF and chronic colonization had anti-PaAb values of 11.6 ± 2.1 ELISA units (EU) and sCD40L in plasma of 1530.9 ±1162.3 pg/mL; those with intermittent infection had 5.7 ± 2.7 EU and 2243.6 ± 1475.9 pg/mL; and those who were never infected had 3.46 ± 1.8 EU (p≤0.001) and 1008.1 ± 746.8 pg/mL (p≤0.01), respectively. The cutoff value of sCD40L of 1255 pg/mL was associated with an area under the ROC (receiver operating characteristic curve) of 0.84 (95% CI, 0.71 to 0.97), reflecting P. aeruginosa infection with a sensitivity of 73% and a specificity of 89%. Lung damage was determined using the Brasfield Score, the Bhalla Score, and spirometry (FVC%, FEV1%) and found to be significantly different among the groups (p≤0.001).ConclusionCirculating sCD40L levels are increased in patients with cystic fibrosis and P. aeruginosa infection. Soluble CD40L appears to reflect infection and provides a tool for monitoring the evolution of lung deterioration.

show abstract

“…The observations that CD154 expressions in L. major-infected susceptible or resistant mouse strains were comparable, and that the CD40-CD154 pathway was involved in IL-12 production, which was found to be impaired in L. major-infected susceptible mouse strain, led to the proposition that there might be a defect in CD40 signaling in Leishmania infection [28,29]. Indeed, it was found that BALB/cderived, thioglycolate-elicited peritoneal macrophages infected with L. major showed, upon CD40 stimulation, a defective inducible nitric oxide synthase (iNOS) induction that was due to an impaired p38MAPK activation.…”

Section: Modulation Of Macrophage Cd40 Signaling By Leishmaniamentioning

confidence: 99%

Macrophage Kinases in Leishmaniasis

Padwal

Sarma

Sudan

et al. 2013

Protein Phosphorylation in Parasites

View full text Add to dashboard Cite

Leishmania is an obligatorily intracellular parasite residing and replicating in mammalian macrophages as amastigotes. Once activated, macrophages destroy Leishmania amastigotes. The macrophages can be activated by stimulating CD40, a costimulatory receptor, with an agonistic antibody or a recombinant CD40-ligand. CD40-induced macrophage activation involves different kinases. CD40 signals reciprocally trigger counteractive effector functions through two mitogen-activated protein kinases: p38MAPK and ERK-1/2. The reciprocity stems from two basic mechanisms. First, CD40 signalosomes in detergent-resistant, cholesterol-rich membrane domains or in detergent-soluble, cholesterol-poor membrane domains trigger p38MAPK or ERK-1/2 activation, respectively. Second, the signaling intermediates that carry the CD40 signals from these two membrane domains are organized in two modules. These intermediates can crosscheck the strength of CD40 signals in each of the bimodular pathways to reroute the signal accordingly. Quantitative analysis reveals that the bimodular architecture of the kinase network is endowed with several properties such as reciprocity, plasticity, and the ability to adjust signal strength in each of the modules. As an evasion strategy, Leishmania inhibits the kinases Lyn, PI3 K, PKCb and p38 MAPK that are used by the host cell to eliminate the parasite, whereas it promotes the activity of Syk, Raf-1, PKC-f and ERK-1/2 that are required for parasite survival. Targeting these kinases -syk, PKCz and ERK-1/2 -resulted in host-protection in a susceptible mouse strain. In this chapter, a novel CD40 signaling system is described that organizes kinases bimodularly to trigger reciprocal and adaptable signals working at the interface of the host and the parasite.

show abstract

CD40 and the immune response to parasitic infections

Cited by 20 publications

References 148 publications

High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis

High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis

A High Level of Soluble CD40L Is Associated with P. aeruginosa Infection in Patients with Cystic Fibrosis

Macrophage Kinases in Leishmaniasis

Contact Info

Product

Resources

About