scholarly journals Synergism ofGamma Interferon and Interleukin-5 in the Control of MurineFilariasis

2003 ◽  
Vol 71 (12) ◽  
pp. 6978-6985 ◽  
Author(s):  
Michael Saeftel ◽  
Manuela Arndt ◽  
Sabine Specht ◽  
Lars Volkmann ◽  
Achim Hoerauf

ABSTRACT There has been a prevailing perception that Th1 and Th2 immune responses induce antagonistic immune effector mechanisms during an infection. We investigated the role of the Th1 cytokine gamma interferon (IFN-γ) and the Th2 cytokine interleukin-5 (IL-5) in murine filariasis infections with the rodent filarial nematode Litomosoides sigmodontis with regard to immune responses to the parasite. Earlier data showed an important role for IL-5 and IFN-γ in effective immune responses to filarial infection. Therefore, in this study it was asked whether IL-5 and IFN-γ act synergistically or antagonistically. Indeed, IL-5 as well as IFN-γ knockout (KO) mice show a higher worm load than the wild-type controls. IFN-γ/IL-5 double-KO mice had a significantly higher worm load than any of the single-KO mice, suggesting a synergism between IFN-γ and IL-5 in controlling worm infection. Neutrophils are known to play an important role for the containment and encapsulation process of the worms. In infected IFN-γ KO, IL-5 KO, and IFN-γ/IL-5 double-KO mice, neutrophils were significantly reduced in chemotactic activity levels compared to controls. In addition, the level of phagocytosis activity of neutrophils from IFN-γ/IL-5 double-KO mice was further decreased in comparison to that of the single-KO mice. Levels of tumor necrosis factor alpha, which is an important factor for neutrophil activation, were found to be reduced in macrophages from KO mice. In conclusion, these results argue for immune effector mechanisms in murine filarial infection that are dependent on both IFN-γ and IL-5. Synergistic effects of the two cytokines may be mediated, at least in part, by neutrophils for the control of adult worms.

2005 ◽  
Vol 73 (12) ◽  
pp. 8369-8380 ◽  
Author(s):  
Kathleen R. Page ◽  
Anne E. Jedlicka ◽  
Benjamin Fakheri ◽  
Gregory S. Noland ◽  
Anup K. Kesavan ◽  
...  

ABSTRACT Malaria and tuberculosis are endemic in many regions of the world, and coinfection with the two pathogens is common. In this study, we examined the effects of long- and short-term infection with Mycobacterium tuberculosis on the course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice, which was especially prominent 5 days after infection with P. yoelii 17XL. Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha than splenocytes from mice infected with either pathogen alone. Interestingly, mycobacterium-induced protection against lethal P. yoelii is mouse strain specific. BALB/c mice were significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL and were not protected against lethal malaria by coinfection with M. tuberculosis. In addition, M. tuberculosis did not augment IFN-γ responses in BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that M. tuberculosis-induced potentiation of type 1 immune responses is associated with protection against lethal murine malaria.


2005 ◽  
Vol 73 (4) ◽  
pp. 2175-2183 ◽  
Author(s):  
Anton Pernthaner ◽  
Sally-Ann Cole ◽  
Lilian Morrison ◽  
Wayne R. Hein

ABSTRACT Cytokine gene expression in cells migrating in afferent and efferent intestinal lymph was monitored for extended time periods in individual sheep experimentally infected with the nematode Trichostrongylus colubriformis. Animals from stable selection lines with increased levels of either genetic resistance (R) or susceptibility (S) to nematode infection were used. Genes for interleukin-5 (IL-5), IL-13, and tumor necrosis factor alpha (TNF-α), but not for IL-4, IL-10, or gamma interferon (IFN-γ), were consistently expressed at higher levels in both afferent and efferent lymph cells of R sheep than in S sheep. However, only minor differences were observed in the surface phenotypes and antigenic and mitogenic responsiveness of cells in intestinal lymph between animals from the two selection lines. The IL-4 and IL-10 genes were expressed at higher levels in afferent lymph cells than in efferent lymph cells throughout the course of the nematode infection in animals of both genotypes, while the proinflammatory TNF-α gene was relatively highly expressed in both lymph types. These relationships notwithstanding, expression of the IL-10 and TNF-α genes declined significantly in afferent lymph cells but not in efferent lymph cells during infection. Collectively, the results showed that R-line sheep developed a strong polarization toward a Th2-type cytokine profile in immune cells migrating in lymph from sites where the immune response to nematodes was initiated, although the IFN-γ gene was also expressed at moderate levels. Genes or alleles that predispose an animal to develop this type of response appear to have segregated with the R selection line and may contribute to the increased resistance of these animals.


2019 ◽  
Vol 9 (4) ◽  
pp. 632-639
Author(s):  
Esmaeil Abasi ◽  
Shahram Shahabi ◽  
Majid Golkar ◽  
Peyman Khezri ◽  
Habib Mohammadzadeh Hajipirloo

Purpose: Propranolol as a novel adjuvant, was used to evaluate the immunogenic effect of threedoses of recombinant SAG-1 (rSAG-1) antigen of Toxoplasma gondii in BALB/c mice for findingthe optimal dose, and was compared with efficacy of tachyzoite lysate antigen (TLA).Methods: Eight different groups of 15 BALB/c mice received different volumes of theimmunogenic material (three doses of r SAG-1 and one dose of TLA antigens), with or withoutpropranolol adjuvant, subcutaneously. The control group mice received only PBS. Three weeksafter the last immunization, the serum levels of IgG2a, IgG1 and IgG total antibodies againstTLA, splenic interleukin-5 (IL-5) and Interferon-gamma (IFN-γ) (produced against TLA) and thesplenic lymphocyte proliferation after adding TLA were measured to evaluate humoral andcellular immune responses. Challenge test was performed by subcutaneously injection of 1000alive and active tachyzoites in to five mice per each group and survival days for each group ofmice were recorded.Results: The mice group that received propranolol adjuvant and 20 μg of r SAG-1 antigenper dose of injection showed significantly more IFN-γ production, more proliferation ofsplenic lymphocytes and higher anti-TLA-specific IgG2a production (three main indexes forcell mediated immunity) in comparison with other groups. Moreover, in the challenge test,this group of mice had a significantly increased survival time, indicating the positive effect ofpropranolol in the more stimulating of cellular immunity that is necessary for toxoplasmosisprevention or suppress.Conclusion: Our results showed that T. gondii rSAG-1 antigen in combination with propranololas adjuvant (which can induce Th1 related responses) are good candidates for further study toa vaccine design.<br />


2000 ◽  
Vol 68 (3) ◽  
pp. 1150-1155 ◽  
Author(s):  
N. R. Jayagopala Reddy ◽  
Bruce N. Wilkie ◽  
Peter Borgs ◽  
Bonnie A. Mallard

ABSTRACT Yorkshire pigs were bred selectively for high and low immune responses (H and L pigs, respectively) based on multiple antibody (Ab) and cell-mediated immune response traits. In a previous experiment, generation 4 (G4) pigs of each line were infected with Mycoplasma hyorhinis. High responders had a more rapid and higher Ab response and less polyserositis, but arthritis was more severe in H pigs than in L pigs. To test the hypothesis that line differences were attributable to differential expression of cytokines, M. hyorhinis infection was induced in pigs of G8. Arthritis was more severe clinically (P, ≤0.05) and postmortem (P, ≤0.001) when M. hyorhinis CFU were more numerous in synovial fluid (SF) of H pigs than of L pigs (P, ≤0.03). In H pigs but not L pigs, CFU and lesion scores were correlated positively. In H pigs, infection increased the frequency of expression of mRNAs for interleukin-8 (IL-8), IL-10, and tumor necrosis factor alpha (TNF-α) in mononuclear cells from synovial membranes (SM). In L pigs, IL-1α, IL-6, IL-10, and TNF-α mRNAs were increased in frequency of expression. The quantity of the cytokine message for IL-6 was increased in infected H pigs. For L pigs, infection increased the cytokine message for IL-1α, IL-6, IL-10, and TNF-α. IL-6 in SM and gamma interferon (IFN-γ) in SF were produced at a higher copy number in H pigs than in L pigs after infection. For H pigs, there were no positive rank correlations between lesion or CFU scores and cytokines. For L pigs, IL-1α, IL-8, IL-10, and TNF-α in SM correlated with CFU, while IL-6, TNF-β, and IFN-γ in SF correlated with CFU. Lesion score in L pigs correlated with IL-1α in SF. While these results indicate that H and L pigs differ in the cytokine response to M. hyorhinis infection, they do not confirm a characteristic cytokine response in association with the relative susceptibility to infection and arthritis observed in H pigs.


2010 ◽  
Vol 78 (5) ◽  
pp. 2257-2263 ◽  
Author(s):  
Shahani Noor ◽  
Andrew S. Habashy ◽  
J. Philip Nance ◽  
Robin T. Clark ◽  
Kiav Nemati ◽  
...  

ABSTRACT The chemokine receptor CCR7 is a well-established homing receptor for dendritic cells and T cells. Interactions with its ligands, CCL19 and CCL21, facilitate priming of immune responses in lymphoid tissue, yet CCR7-independent immune responses can be generated in the presence of sufficient antigen. In these studies, we investigated the role of CCR7 signaling in the generation of protective immune responses to the intracellular protozoan parasite Toxoplasma gondii. The results demonstrated a significant increase in the expression of CCL19, CCL21, and CCR7 in peripheral and central nervous system (CNS) tissues over the course of infection. Unexpectedly, despite the presence of abundant antigen, CCR7 was an absolute requirement for protective immunity to T. gondii, as CCR7−/− mice succumbed to the parasite early in the acute phase of infection. Although serum levels of interleukin 12 (IL-12), IL-6, tumor necrosis factor alpha (TNF-α), and IL-10 remained unchanged, there was a significant decrease in CCL2/monocyte chemoattractant protein 1 (MCP-1) and inflammatory monocyte recruitment to the site of infection. In addition, CCR7−/− mice failed to produce sufficient gamma interferon (IFN-γ), a critical Th1-associated effector cytokine required to control parasite replication. As a result, there was increased parasite dissemination and a significant increase in parasite burden in the lungs, livers, and brains of infected mice. Adoptive-transfer experiments revealed that expression of CCR7 on the T-cell compartment alone is sufficient to enable T-cell priming, increase IFN-γ production, and allow the survival of CCR7−/− mice. These data demonstrate an absolute requirement for T-cell expression of CCR7 for the generation of protective immune responses to Toxoplasma infection.


Author(s):  
Alberto Comes ◽  
Emma Di Carlo ◽  
Piero Musiani ◽  
Ombretta Rosso ◽  
Raffaella Meazza ◽  
...  

2004 ◽  
Vol 72 (5) ◽  
pp. 2679-2688 ◽  
Author(s):  
A. Rial ◽  
D. Lens ◽  
L. Betancor ◽  
H. Benkiel ◽  
J. S. Silva ◽  
...  

ABSTRACT Nonspecific stimulation of lung defenses by repeated oral administration of immunomodulators, such as bacterial extracts, has shown potential for the prevention of respiratory tract infections. Here, we show that intranasal (i.n.) immunization with a bacterial extract formulated as a colloid induces an acute inflammatory response in the lungs characterized by increased production of CCL and CXCL chemokines and a major influx of dendritic cells (DCs) and neutrophils, with a higher proportion of DCs showing an activated phenotype (high CD80/CD86 expression). Cytokine levels measured in bronchoalveolar-lavage samples showed a small increase in the production of tumor necrosis factor alpha and similar levels of the other cytokines measured (interleukin 10 [IL-10], IL-12, and gamma interferon [IFN-γ]) in immunized mice compared with control mice. However, the recall response of primed animals after antigenic challenge induced increased expression of IL-12 and IFN-γ mRNAs in lung homogenates. Overall, all these effects were not due to the lipopolysaccharide content in the bacterial extract. Furthermore, we found that three i.n. doses administered 2 to 3 weeks apart were enough to elicit long-lasting specific serum immunoglobulin G (IgG) and secretory IgA antibody responses. Assessment of IgG subclasses showed a balanced pattern of IgG1-IgG2a responses. The serum total IgE concentrations were also elevated in immunized mice 2 weeks after the third dose, but they significantly decreased soon afterwards. Our results suggest that simple formulations of bacterial extracts administered i.n. are highly immunogenic, eliciting local and systemic immune responses, and may serve as the basis for cost-effective immunotherapies for the prevention and treatment of respiratory infections.


2009 ◽  
Vol 17 (2) ◽  
pp. 258-262 ◽  
Author(s):  
Françoise Vermeulen ◽  
Virginie Verscheure ◽  
Eliane Damis ◽  
Danièle Vermeylen ◽  
Gaëlle Leloux ◽  
...  

ABSTRACT Based on studies reporting specific antibody titers, it is recommended to vaccinate preterm infants against Bordetella pertussis according to their chronological age. However, as specific T-cell responses also are involved in the protection against B. pertussis, we have determined whether highly preterm infants (<31 weeks) are able to mount these immune responses during vaccination. Forty-eight premature infants were vaccinated at 2, 3, and 4 months of their chronological age with an acellular (Pa; n = 24) or a whole-cell (Pw; n = 24) tetravalent diphtheria-tetanus-pertussis-polio vaccine, and blood samples were collected at 2, 3, and 6 months of age. Most of the Pa- and Pw-vaccinated infants developed at 3 or 6 months of age a gamma interferon (IFN-γ) response to the B. pertussis antigens, accompanied by an interleukin-5 (IL-5) and IL-13 secretion for the Pa-vaccinated infants. No association was found between a very low infant birth weight, the occurrence of severe infections, and corticosteroid treatment or the administration of gammaglobulins with a low level of antigen-induced IFN-γ secretion. We conclude that like full-term infants, most preterm infants are able to mount a specific cellular immune response to the administration of the first doses of an acellular or a whole-cell pertussis vaccine.


2007 ◽  
Vol 15 (2) ◽  
pp. 303-307 ◽  
Author(s):  
Jianhua Sun ◽  
Xiaoming Song ◽  
Songhua Hu

ABSTRACT The combined adjuvant effect of ginsenoside Rg1 and aluminum hydroxide (alum) on immune responses to ovalbumin (OVA) in mice was investigated. BALB/c mice were subcutaneously (s.c.) inoculated twice with OVA alone or in combination with Rg1, alum, or Rg1 plus alum. Samples were collected 2 weeks after the boosting for the measurement of anti-OVA immunoglobulin G (IgG) isotypes in sera and gamma interferon (IFN-γ) and interleukin-5 (IL-5) produced in singular splenocyte cultures. Delayed-type hypersensitivity (DTH) responses were measured in mice immunized as described above. After 10 days, the mice were injected s.c. with OVA at the footpads. Thereafter, the thickness of the footpads was measured once daily for 5 days. The results indicated that alum enhanced mainly Th2 (IgG1 and IL-5) responses (P < 0.05), while Rg1 enhanced both Th1 (IgG1 and IL-5) and Th2 (IgG2a, IFN-γ, and DTH) responses (P < 0.05). The highest immune responses were found in the mice injected with OVA solution containing both alum and Rg1. In addition, the hemolytic activity of Rg1 was much lower than that of Quil A. Therefore, Rg1 deserves further studies in order to tailor desired immune responses when a mixed Th1/Th2 immune response is needed.


2008 ◽  
Vol 76 (9) ◽  
pp. 4190-4198 ◽  
Author(s):  
R. Al-Attiyah ◽  
A. S. Mustafa

ABSTRACT Comparative genomics has identified several regions of differences (RDs) between the infectious Mycobacterium tuberculosis and the vaccine strains of Mycobacterium bovis BCG. We aimed to evaluate the cellular immune responses induced by antigens encoded by genes predicted in 11 RDs. Synthetic peptides covering the sequences of RD1, RD4 to RD7, RD9 to RD13, and RD15 were tested for antigen-induced proliferation and secretion of Th1 cytokine, gamma interferon (IFN-γ), by peripheral blood mononuclear cells (PBMC) obtained from culture-proven pulmonary tuberculosis (TB) patients and M. bovis BCG-vaccinated healthy subjects. Among the peptide pools, RD1 induced the best responses in both donor groups and in both assays. In addition, testing of TB patients' PBMC for secretion of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], IL-8, and IL-1β), Th1 cytokines (IFN-γ, IL-2, and TNF-β), and Th2 cytokines (IL-4, IL-5, and IL-10) showed differential effects of RD peptides in the secretion of IFN-γ and IL-10, with high IFN-γ/IL-10 ratios (32 to 5.0) in response to RD1, RD5, RD7, RD9, and RD10 and low IFN-γ/IL-10 ratios (<1.0) in response to RD12, RD13, and RD15. Peptide-mixing experiments with PBMC from healthy subjects showed that secretion of large quantities of IL-10 in response to RD12 and RD13 correlated with inhibition of Th1 responses induced by RD1 peptides. In conclusion, our results suggest that M. tuberculosis RDs can be divided into two major groups—one group that activates PBMC to preferentially secrete IFN-γ and another group that activates preferential secretion of IL-10—and that these two groups of RDs may have roles in protection against and pathogenesis of TB, respectively.


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