Role of lymphocytes in macrophage-induced killing of Coccidioides immitis in vitro

Beaman, L; Benjamini, E.; Pappagianis, Demosthenes

doi:10.1128/iai.34.2.347-353.1981

Cited by 52 publications

(27 citation statements)

References 19 publications

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“…If antibody does not play a role in acquired immunity, then perhaps one must postulate a protective role for cell-mediated immunity, as has been clearly demonstrated for coccidioidomycosis (2). The results of the lymphocyte proliferation and footpad assays demonstrated clearly that all six strains were capable of mounting cell-mediated responses to antigens from C. albicans.…”

Section: Discussionmentioning

confidence: 89%

Immune Responses to Candida albicans in Genetically Distinct Mice

1982

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Mice from six genetically distinct strains were examined for their immune responses to Candida albicans in in vitro and in vivo assays, and naive mice and mice immunized with the fungus were challenged intravenously with three different doses of C. albicans to determine differences in susceptibility. Naive mice from the six groups showed substantial differences in resistance to challenge based on mortalities and quantitative cultures of kidneys, with mice from strains C57BL/6J and BALB/cByJ showing the most resistance; mice from strains A/J, C3H/HeJ, and CBA/J showing moderate susceptibility; and mice from strain DBA/2J showing the highest degree of susceptibility to challenge. Unimmunized mice from strains C57BL/6J and BALB/cByJ did not produce detectable levels of Candida-specific antibody by the end of the 28-day observation period when challenged intravenously, but the other strains did. Immunized mice showed a degree of protection to challenge, with all groups except mice from strain BALB/cByJ showing a reduction of two to three log units in the level of colonization in their kidneys and all strains producing significant levels of antibody. Additionally, the immunized mice of all strains developed substantial levels of delayed-type hypersensitivity and demonstrated nearly identical lymphocyte proliferative responses to Candida antigens. The results indicate that resistance to systemic candidiasis is dependent upon a combination of innate factors, predominately an intact complement system, and the acquisition of an immune response, most likely of a cell-mediated type. Additionally, the findings suggest that genetic control of acquired resistance to C. albicans may not be associated with the H-2 complex.

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Section: Discussionmentioning

confidence: 89%

Immune Responses to Candida albicans in Genetically Distinct Mice

1982

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“…However, a significant increase in phagosome-lysosome fusion was observed in macrophages infected in the presence of antigen-activated immune lymphocytes. This correlated with the ability of macrophages to kill C. immitis (3).…”

mentioning

confidence: 82%

“…It was shown that adoptive transfer of resistance to infection with C. immitis was dependent on T lymphocytes from mice immunized with spherule vaccine (4). In vitro, T lymphocytes appeared to promote the antifungal action of macrophages (3). Both arthroconidia and endospores are readily phagocytized by macrophages from normal animals; however, neither are killed.…”

mentioning

confidence: 97%

Activation of macrophages by lymphokines: enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis

Beaman¹,

Benjamini²,

Pappagianis³

1983

Infect Immun

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Previously, it was shown that arthroconidia of Coccidioides immitis appear to inhibit phagosome-lysosome fusion and survive within normal mouse peritoneal macrophages. However, when these macrophages are exposed to antigen-stimulated T lymphocytes from immune mice, activation occurs, leading to enhanced phagosome-lysosome fusion and killing of C. immitis. Results indicate that the activation of macrophages can be effected after incubation with soluble lymphocyte product(s) (lymphokines). The activation of macrophages results if the macrophages are exposed to the lymphokine before, but not after, infection. The results indicate that the lymphocyte population responsible for the elaboration of the lymphokine is phenotypically Lytl 2-and that activation of macrophages by the lymphokine can occur across H-2 histocompatibility barriers.

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“…Early data showed that the endospore-containing phagosomes of peritoneal macrophages were not stained with acridine orange, a fluorescent cationic dye, which is an indicator of acidic organelles. 2 In contrast, macrophages obtained from mice vaccinated with formalin-killed spherules stained positively with acridine orange and contained endospores with reduced fungal viability in vitro. 3 The inability of macrophages from nonvaccinated mice to kill endospores has been suggested to be at least partly due to the inhibition of lysosomal fusion, which may explain the negative results of acridine orange staining of the phagocytes.…”

Section: Induction Of Host Arginase I Production Compromises Host Defmentioning

confidence: 97%

Virulence Mechanisms of Coccidioides

Hung

Xue

Cole

2007

Annals of the New York Academy of Sciences

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Coccidioides is a fungal respiratory pathogen of humans that can cause disease in both immunosuppressed and immunocompetent individuals. We describe here three mechanisms by which the pathogen survives in the hostile host environment: production of a dominant spherule outer wall glycoprotein (SOWgp) that modulates host immune response and results in compromised cell-mediated immunity to coccidioidal infection, depletion of SOWgp presentation on the surface of endospores, which prevents host recognition of the pathogen when the fungal cells are most vulnerable to phagocytic defenses, and induction of elevated production of host arginase I and coccidioidal urease, which contribute to tissue damage at sites of infection. Arginase I competes with inducible nitric oxide synthase (iNOS) in macrophages for the common substrate, L-arginine, and thereby reduces nitric oxide (NO) production and increases the synthesis of host orinithine and urea. Host-derived L-ornithine may promote pathogen growth and proliferation by providing a pool of the monoamine, which could be taken up and used for synthesis of polyamines via metabolic pathways of the parasitic cells. We have shown that high concentrations of Coccidioides- and host-derived urea at infection sites in the presence of urease produced and released by the pathogen, results in secretion of ammonia and contributes to alkalinization of the microenvironment. We propose that ammonia and enzymatically active urease released from spherules during the parasitic cycle of Coccidioides exacerbate the severity of coccidioidal infection by contributing to a compromised immune response to infection and damage of host tissue at foci of infection.

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Role of lymphocytes in macrophage-induced killing of Coccidioides immitis in vitro

Cited by 52 publications

References 19 publications

Immune Responses to Candida albicans in Genetically Distinct Mice

Immune Responses to Candida albicans in Genetically Distinct Mice

Activation of macrophages by lymphokines: enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis

Virulence Mechanisms of Coccidioides

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