In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.

ABSTRACT A vaccine for human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we constructed single-cycle simian immunodeficiency viruses (SIVs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (IFN-γ) as a potential vaccine strategy. We previously showed that IFN-γ expression by pseudotyped SIVs does not alter viral single-cycle infectivity. T cells primed with dendritic cells transduced by pseudotyped SIVs expressing high levels of IFN-γ had stronger T-cell responses than those primed with dendritic cells transduced by constructs lacking IFN-γ. In the present study, we tested the immunogenicities of these pseudotyped SIVs in a rat model. The construct expressing low levels of rat IFN-γ (dSIVLRγ) induced higher levels of cell-mediated and humoral immune responses than the construct lacking IFN-γ (dSIVR). Rats vaccinated with dSIVLRγ also had lower viral loads than those vaccinated with dSIVR when inoculated with a recombinant vaccinia virus expressing SIV Gag-Pol as a surrogate challenge. The construct expressing high levels of IFN-γ (dSIVHRγ) did not further enhance immunity and was less protective than dSIVLRγ. In conclusion, the data indicated that IFN-γ functioned as an adjuvant to augment antigen-specific immune responses in a dose- and cell type-related manner in vivo. Thus, fine-tuning of the cytokine expression appears to be essential in designing vaccine vectors expressing adjuvant genes such as the gene for IFN-γ. Furthermore, we provide evidence of the utility of the rat model to evaluate the immunogenicities of single-cycle HIV/SIV recombinant vaccines before initiating studies with nonhuman primate models.

Download Full-text

Candida Albicans Activated Splenocytes Promote Strong Immune Responses in a Murine Model of Breast Cancer

Basic & Clinical Cancer Research ◽

10.18502/bccr.v11i3.5719 ◽

2021 ◽

Author(s):

Siavash Mashhouri ◽

Erfan Yarahmadi ◽

Seyyed Meysam Abtahi Froushani

Keyword(s):

Breast Cancer ◽

Candida Albicans ◽

Immune Responses ◽

Survival Curve ◽

Tumor Development ◽

Yeast Form ◽

Tumor Bearing ◽

4T1 Cells ◽

Breast Cancer Growth

Background: The potential of Candida albicans to modulate antigen-presenting cells maturation has been documented in past studies. Dendritic cells are critical modulators in the orchestration of adaptive immune responses alongside myeloid subtypes, which play an important role in the presentation of antigens to T cells. The aim of this study was to evaluate the efficacy of splenocytes activated with the extract of heated 4T1 cells and the yeast form of C. albicans against breast cancer growth in vivo. Methods: 4T1 cells were subcutaneously injected into the left flanks of female BALB/c mice (n=40). At a time when palpable tumors had developed, experimental groups were immunized twice at one-week interim with either activated splenocytes with the extract of heated 4T1 or the killed preparation of yeast form of C. albicans or a combination of the two-One week after the second injection, one-half of animals (n=20) were euthanized to investigate the immune response profile. Results: Administration of activated splenocytes with the combination protocol caused a favorable survival curve and slower rates of tumor development compared to other tumor-bearing mice. Moreover, combination therapy significantly increased the secretion of IFN-γ, respiratory burst and nitric oxide production and conversely diminished the secretion of IL-4, IL-10 and TGF-β in the splenocyte population. Conclusion: Since the murine 4T1 cell line is similar to the final stage of human breast carcinoma, we postulate that activated splenocytes with the extract of heated 4T1 cells and yeast form of C. albicans can reduce tumor development in tumor-bearing mice.

Download Full-text

Mannan Antigen of Candida Albicans and Cellular Immune Responses in Vitro and in Vivo

Fungal Antigens ◽

10.1007/978-1-4613-0773-0_13 ◽

1988 ◽

pp. 185-196

Author(s):

Anne Durandy ◽

Alain Fischer ◽

Edouard Drouhet ◽

Claude Griscelli

Keyword(s):

Candida Albicans ◽

Immune Responses ◽

Cellular Immune Responses ◽

Cellular Immune

Download Full-text

Candida albicans and Candida krusei Differentially Induce Human Blood Mononuclear Cell Interleukin-12 and Gamma Interferon Production

Infection and Immunity ◽

10.1128/iai.68.5.2464-2469.2000 ◽

2000 ◽

Vol 68 (5) ◽

pp. 2464-2469 ◽

Cited By ~ 28

Author(s):

Jingbo Xiong ◽

Kefei Kang ◽

Liming Liu ◽

Yuichi Yoshida ◽

Kevin D. Cooper ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Candida Albicans ◽

Immune Responses ◽

Human Blood ◽

Gamma Interferon ◽

Candida Krusei ◽

Type I ◽

Human Monocytes ◽

Ifn Γ

ABSTRACT Protection against Candida infection involves both innate and acquired immune responses, and cytokines produced by monocytes during the innate response may modify the acquired immune response by T cells. We hypothesized that Candida species which differ in pathogenicity can differentially induce production of immunoregulatory cytokines by human monocytes, which in turn modify T cells for immune responses to Candida. To test this hypothesis, we examined the effects of Candida albicans andCandida krusei on immunoregulatory cytokine production by human monocytes and gamma interferon (IFN-γ) production by peripheral blood mononuclear cells (PBMC). Purified monocytes were incubated with live or heat-killed strains of C. albicans and C. krusei at the optimal Candida/monocyte ratio of 0.5. Cytokines in the supernatants were measured by enzyme-linked immunosorbent assay. Our data demonstrated that live C. albicans and C. krusei significantly induced interleukin-10 (IL-10), monocyte chemotactic factor 1, IL-1β, and tumor necrosis factor alpha production by monocytes relative to unstimulated monocytes. In contrast, unlike C. krusei, pathogenic live strains of C. albicans induced no or only a minimal level of IL-12. The expression of IL-12 p40 mRNA levels by reverse transcription-PCR corroborated the IL-12 protein (p70) findings. In human PBMC, human blood monocytes were the major source of both IL-10 and IL-12 production in response to C. albicansand C. krusei. Upon activation of T cells in the presence of Candida-modified monocytes and antigen-presenting cells, IL-12 production by PBMC treated with Candida organisms correlated strongly with the level of IFN-γ production by T cells. These results indicate that the virulence of C. albicansmay be related to its ability to induce the monocytic type II cytokine IL-10, with a selective inhibition of IL-12 production, which may be responsible for the observed lack of T-cell IFN-γ and may restrain an effective type I immune response to Candida.

Download Full-text

Effect of in vivo administration of recombinant murine gamma interferon on in vitro lymphoproliferative responses following immunization with Candida albicans.

Infection and Immunity ◽

10.1128/iai.60.5.1927-1935.1992 ◽

1992 ◽

Vol 60 (5) ◽

pp. 1927-1935 ◽

Cited By ~ 2

Author(s):

R E Garner ◽

U Kuruganti ◽

L A al-Hussaini ◽

C W Czarniecki ◽

J E Domer

Keyword(s):

Candida Albicans ◽

Gamma Interferon ◽

In Vivo Administration

Download Full-text

Alterations in Frequency of Interleukin-2 (IL-2)-, Gamma Interferon-, or IL-4-Secreting Splenocytes Induced by Candida albicans Mannan and/or Monophosphoryl Lipid A

Infection and Immunity ◽

10.1128/iai.66.4.1392-1399.1998 ◽

1998 ◽

Vol 66 (4) ◽

pp. 1392-1399 ◽

Cited By ~ 9

Author(s):

Shaokang P. Li ◽

Sang-il Lee ◽

Judith E. Domer

Keyword(s):

Candida Albicans ◽

Lipid A ◽

Interleukin 2 ◽

Gamma Interferon ◽

Saline Control ◽

Immunomodulatory Activity ◽

Monophosphoryl Lipid A ◽

Monophosphoryl Lipid

ABSTRACT We have shown previously that intravenous injection ofCandida albicans mannan (MAN) into naive mice induced CD8+ effector downregulatory cells and that such cells were not produced if mice were deficient in CD4+ or I-A+ cells during the early interval (≤30 h) following the introduction of MAN. Moreover, the nonspecific biological response modifier monophosphoryl lipid A (MPL), given in vivo or incubated with cells in vitro, can abrogate the MAN-specific immunomodulatory activity. The mechanism by which the abrogation is mediated is unknown, but it is hypothesized to involve cytokines. Therefore, we measured the number of cytokine-secreting cells for the Th1 cytokine interleukin-2 (IL-2) and the Th2 cytokine IL-4, as well as for gamma interferon (IFN-γ), in splenocyte populations from MAN and/or MPL-treated mice, using an enzyme-linked immunospot assay designed to detect individual cytokine-secreting cells (spot-forming cells [SFC]). Cytokine-secreting cells were demonstrated in cell suspensions enriched for CD4+ cells, but no SFC could be demonstrated in populations enriched for CD8+ cells. Both MAN and MPL, when administered to separate groups of animals, stimulated the production of increased numbers of cytokine-producing cells for each of the three cytokines tested. The response with respect to IL-4-secreting cells, however, was the most striking. Despite the fact that MAN and MPL independently caused increases in SFC to all three cytokines, when both MAN and MPL were administered to the same animal, all increases were reversed, and the numbers of SFC detected were at or below those detected in saline control animals. These data support the hypothesis that IL-4 is involved in MAN-specific immunoregulatory activities. The data also emphasize the fact that two immunomodulators, i.e., MAN and MPL, having similar effects when given in vivo independently, may be antagonistic when administered sequentially to the same animal.

Download Full-text

Reduced in vivo Cell-mediated Immune Responses to Mumps, Tuberculin, and Streptokinase/Streptodornase but not to Candida albicans in Oral Lichen Planus

Journal of Dental Research ◽

10.1177/00220345990780110701 ◽

1999 ◽

Vol 78 (11) ◽

pp. 1704-1710 ◽

Cited By ~ 6

Author(s):

C. Simark-Mattsson ◽

M. Jontell ◽

G. Bergenholtz ◽

U.I. Dahlgren

Keyword(s):

Candida Albicans ◽

Immune Responses ◽

Lichen Planus ◽

Oral Lichen Planus ◽

Oral Lichen

Download Full-text

Characteristics of Invasive Candidiasis in Gamma Interferon- and Interleukin-4-Deficient Mice: Role of Macrophages in Host Defense against Candida albicans

Infection and Immunity ◽

10.1128/iai.66.4.1708-1717.1998 ◽

1998 ◽

Vol 66 (4) ◽

pp. 1708-1717 ◽

Cited By ~ 71

Author(s):

Rita Káposzta ◽

Peter Tree ◽

László Maródi ◽

Siamon Gordon

Keyword(s):

Candida Albicans ◽

Host Defense ◽

Invasive Candidiasis ◽

Critical Role ◽

Gamma Interferon ◽

Interleukin 4 ◽

In Vivo Studies ◽

Mouse Strains ◽

Ifn Γ

ABSTRACT Murine models of invasive candidiasis were used to study the in vivo importance of gamma interferon (IFN-γ) and interleukin-4 (IL-4) in host defense against Candida albicans and to characterize the tissue inflammatory reactions, with special reference to macrophages (Mφ). Knockout (KO) IFN-γ-deficient (GKO) and IL-4-deficient (IL-4 KO) and C57BL/6 parental mouse strains were challenged intraperitoneally with 108 C. albicans blastoconidia. Survival of GKO mice was significantly lower (16.7%) than that of C57BL/6 control (55.5%) and IL-4 KO (61.1%) animals, but was not correlated with the extent of organ colonization. Immunohistological analysis with a panel of myeloid and lymphoid markers revealed multiple renal abscesses, myocarditis, hepatitis, meningoencephalitis, and pneumonia in each strain, with a dominant presence of Mφ. In the absence of IFN-γ, C. albicans induced striking changes in the phenotype of alveolar Mφ and extensive perivascular lymphoid infiltrates in the lung. Impairment in nitric oxide production by peritoneal Mφ was shown only in GKO mice, and they produced Candida-specific immunoglobulin G (IgG), IgM, IgA, and IgG subclasses in lower titers. Our in vivo studies with KO mice elucidate a critical role for IFN-γ, but not IL-4, in host defense against C. albicans.

Download Full-text