Endogenous Pro- and Anti-Inflammatory Cytokines Differentially Regulate an In Vivo Humoral Response to<i>Streptococcus pneumoniae</i>

Khan, Abdul Qayyum; Shen, Yi; Wu, Zheng-Qi; Wynn, Thomas A.; Snapper, Clifford M.

doi:10.1128/iai.70.2.749-761.2002

Cited by 85 publications

(85 citation statements)

References 85 publications

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“…In the absence of adjuvant, IL-6 KO mice secreted a reduced amount of NP-specific Abs compared with the WT mice (Fig. 2E, white histograms), in agreement with previous reports (31). However, oligomycin coinjection with NP-KLH elicited a strong increase in Ab titers in both WT and IL-6 KO mice, suggesting an IL-6-independent mechanism for the humoral responses induced by oligomycin.…”

Section: Oligomycin Increases Humoral Responses Independently Of Nlrpsupporting

confidence: 80%

Metabolic Stress Boosts Humoral Responses In Vivo Independently of Inflammasome and Inflammatory Reaction

Andris

Denanglaire

Baus

et al. 2011

The Journal of Immunology

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Adjuvant formulations boost humoral responses by acting through several, yet incompletely elucidated pathways. In this study, we show that oligomycin or 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR) enhances Ab production when coinjected with T cell-dependent Ags. Oligomycin and AICAR lead to intracellular ATP reduction, suggesting that metabolic stress could be sensed by immune cells and leads to increased humoral responses. AICAR promotes IL-4 and IL-21 by naive Th cells but does not affect dendritic cell activation/maturation in vitro or in vivo. Accordingly, the adjuvant effect of AICAR or oligomycin does not require MyD88 or caspase-1 expression in vivo. Because AICAR is well tolerated in humans, this compound could represent a novel and safe adjuvant promoting humoral responses in vivo with a minimal reactogenicity.

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Section: Oligomycin Increases Humoral Responses Independently Of Nlrpsupporting

confidence: 80%

Metabolic Stress Boosts Humoral Responses In Vivo Independently of Inflammasome and Inflammatory Reaction

Andris

Denanglaire

Baus

et al. 2011

The Journal of Immunology

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“…Antibody titers against pneumococcal proteins were increased compared with those in wild-type mice. 41 Although no association was observed between the IL10 polymorphism and specific antibody levels in our population, one might expect a similar effect. Possibly, the concentration of IL-10 in low producers is sufficient to preclude finding differences in antibody titers.…”

Section: Discussionmentioning

confidence: 63%

Genetic Polymorphisms in Immunoresponse GenesTNFA,IL6,IL10, andTLR4Are Associated With Recurrent Acute Otitis Media

et al. 2007

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OBJECTIVE. Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS. DNA samples from 348 children with ≥2 acute otitis media episodes, who were participating in a randomized, controlled vaccination trial, and 463 healthy adult controls were included. Polymorphisms in TNFA, IL1B, IL4, IL6, IL10, IL8, NOS2A, C1INH, PARP, TLR2, and TLR4 were genotyped. Genotype distributions in children with recurrent acute otitis media were compared with those in controls. Within the patient group, the number of acute otitis media episodes before vaccination and the clinical and immunologic response to pneumococcal conjugate vaccinations were analyzed. RESULTS. The IL6-174 G/G genotype was overrepresented in children with acute otitis media when compared with controls. In the patient group, TNFA promoter genotypes −238 G/G and −376 G/G and the TLR4 299 A/A genotype were associated with an otitis-prone condition. Furthermore, lower specific anticapsular antibody production after complete vaccination was observed in patients with the TNFA-238 G/G genotype or TNFA-863 A allele carriage. Finally, the IL10-1082 A/A genotype contributed to protection from the recurrence of acute otitis media after pneumococcal vaccination. CONCLUSIONS. Variation in innate immunoresponse genes such as TNFA-863A, TNFA-376G, TNFA-238G, IL10-1082 A, and IL6-174G alleles in the promoter sequences may result in altered cytokine production that leads to altered inflammatory responses and, hence, contributes to an otitis-prone condition.

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“…We also observed an increment in total anti-PspA IgG in IL-4 KO mice immunized with either rPspA3NS or pSec-pspA3NS compared to WT animals. Higher antibody responses to PspA have previously been observed in IL-4 KO mice than in WT mice, and this is assumed to be due to the lack of suppression of the IgG response by IL-4 (14). In our present studies, we also analyzed the IgG1/IgG2a ratio, and only WT mice immunized with recombinant protein showed a marked predominance of IgG1 (IgG1/IgG2a ratio ϭ 1,024), while balanced IgG1/IgG2a ratios were observed for the other groups (ratio of 4 for pSecpspA3NS-immunized WT mice, 2 for rPspA3NS-immunized IL-4 KO mice, and 0.1 for pSec-pspA3NS-immunized IL-4 KO mice).…”

Section: Discussionmentioning

confidence: 99%

“…Interleukin-12 (IL-12) deficiency has also been correlated with increased susceptibility to pneumococcal infections, presumably due to a deficient T-cell response (10). In mice, the development of disease and the host response to the pneumococcal challenge have been studied with different strains of wild-type (WT) and knockout (KO) animals (13,14,18,25,27), but all of these studies were performed with nonimmunized mice only and reported that resolution of infection in the naïve host is mediated primarily through phagocytosis and intracellular killing by neutrophils and macrophages, which are recruited to the site of infection in response to proinflammatory cytokine and interleukin release by T lymphocytes. In accordance with this, it has been suggested that gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) produced by NK and T cells have a crucial involvement not only in the natural host defense but also in acquired resistance against S. pneumoniae (12,24).…”

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confidence: 99%

Optimized Immune Response Elicited by a DNA Vaccine Expressing Pneumococcal Surface Protein A Is Characterized by a Balanced Immunoglobulin G1 (IgG1)/IgG2a Ratio and Proinflammatory Cytokine Production

Ferreira

Darrieux

Oliveira

et al. 2008

Clin Vaccine Immunol

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We have previously shown that DNA immunization with PspA (pneumococcal surface protein A) DNA is able to elicit protection comparable to that elicited by immunization with PspA protein (with alum as adjuvant), even though the antibody levels elicited by DNA immunization are lower than those elicited by immunization with the protein. This work aims at characterizing the ability of sera to bind to the pneumococcal surface and to mediate complement deposition, using BALB/c wild-type and interleukin-4 knockout mice. We observed that higher anti-PspA levels correlated with intense antibody binding to the pneumococcal surface, while elevated complement deposition was observed with sera that presented balanced immunoglobulin G1 (IgG1)/IgG2a ratios, such as those from DNA-immunized mice. Furthermore, we demonstrated that gamma interferon and tumor necrosis factor alpha were strongly induced after intraperitoneal pneumococcal challenge only in mice immunized with the DNA vaccine. We therefore postulate that although both DNA and recombinant protein immunizations are able to protect mice against intraperitoneal pneumococcal challenge, an optimized response would be achieved by using a DNA vaccine and other strategies capable of inducing balanced Th1/Th2 responses.

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Endogenous Pro- and Anti-Inflammatory Cytokines Differentially Regulate an In Vivo Humoral Response toStreptococcus pneumoniae

Cited by 85 publications

References 85 publications

Metabolic Stress Boosts Humoral Responses In Vivo Independently of Inflammasome and Inflammatory Reaction

Metabolic Stress Boosts Humoral Responses In Vivo Independently of Inflammasome and Inflammatory Reaction

Genetic Polymorphisms in Immunoresponse GenesTNFA,IL6,IL10, andTLR4Are Associated With Recurrent Acute Otitis Media

Optimized Immune Response Elicited by a DNA Vaccine Expressing Pneumococcal Surface Protein A Is Characterized by a Balanced Immunoglobulin G1 (IgG1)/IgG2a Ratio and Proinflammatory Cytokine Production

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