Studies on mediators of cellular immunity in experimental coccidioidomycosis

Kashkin, K. P.; Likholetov, S.M.; Lipnitsky, A. V.

doi:10.1080/00362177785190111

Cited by 12 publications

(5 citation statements)

References 18 publications

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“…However, evidence that the T lymphocytes directly affected the spores was not obtained. This inability to demonstrate killing of C. immitis by lymphocytes conflicts with the earlier conclusions of Kashkin et al (15), which suggested that factors fungicidal for C. immitis were present in supernatants from immune guinea pig lymphocytes. However, although there may be such a difference between the mouse and guinea pig systems, it is difficult to ascribe the effect observed by Kashkin et al (15) simply to the immune guinea pig lymphocytes, since the buffy coat used by these workers likely contained other leukocytes present in the peripheral blood.…”

Section: Discussioncontrasting

confidence: 52%

“…Peritoneal macrophages from guinea pigs, when infected in the presence of lymphocytes from immune animals, phagocytized arthroconidia, and it was thought that the lymphocytes elaborated fungicidal factors which decreased the viability of the phagocytized spores (15). Beaman et al demonstrated that T lymphocytes from immune mice were essential for the transfer of resistance to a lethal infection to a nornal host (5); however, the cells which actually kill C. immitis in immune mice were not defined.…”

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confidence: 99%

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

Beaman¹,

Benjamini²,

Pappagianis

1981

Infect Immun

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Peritoneal macrophages from normal mice phagocytized arthroconidia and endospores of Coccidioides immitis without affecting the viability of the spores within 4 h after infection. In contrast, macrophages, when infected in the presence of lymphocytes from immune mice, significantly reduced the viability of phagocytized endospores and arthroconidia. The inability of macrophages from normal mice to kill C. immitis may in part be explained by the observation that C. immitis appeared to inhibit fusion of the phagosomes containing fungal spores with the lysosomes within the macrophages. However, fusion of phagosomes containing spores and lysosomes was observed in macrophages infected in the presence of lymphocytes from immune mice.

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Section: Discussioncontrasting

confidence: 52%

mentioning

confidence: 99%

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

Beaman¹,

Benjamini²,

Pappagianis

1981

Infect Immun

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“…Kashkin et al (158) reported that peritoneal macrophages from nonimmune guinea pigs phagocytized but did not kill arthroconidia. The relative inefficacy of nonimmune macrophages in killing Coccidioides was confirmed by Beaman et al (20)(21)(22)(23)(24).…”

Section: Host Defenses In Humans Innate Immunitymentioning

confidence: 99%

Coccidioidomycosis: Host Response and Vaccine Development

2004

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Coccidioidomycosis is caused by the dimorphic fungi in the genus Coccidioides. These fungi live as mycelia in the soil of desert areas of the American Southwest, and when the infectious spores, the arthroconidia, are inhaled, they convert into the parasitic spherule/endospore phase. Most infections are mild, but these organisms are frank pathogens and can cause severe lethal disease in fully immunocompetent individuals. While there is increased risk of disseminated disease in certain racial groups and immunocompromised persons, the fact that there are hosts who contain the initial infection and exhibit long-term immunity to reinfection supports the hypothesis that a vaccine against these pathogens is feasible. Multiple studies have shown that protective immunity against primary disease is associated with T-helper 1 (Th-1)-associated immune responses. The single best vaccine in animal models, formalin-killed spherules (FKS), was tested in a human trial but was not found to be significantly protective. This result has prompted studies to better define immunodominant Coccidioides antigen with the thought that a subunit vaccine would be protective. These efforts have defined multiple candidates, but the single best individual immunogen is the protein termed antigen 2/proline-rich antigen (Ag2/PRA). Studies in multiple laboratories have shown that Ag2/PRA as both protein and genetic vaccines provides significant protection against mice challenged systemically with Coccidioides. Unfortunately, compared to the FKS vaccine, it is significantly less protective as measured by both assays of reduction in fungal CFU and assays of survival. The capacity of Ag2/PRA to induce only partial protection was emphasized when animals were challenged intranasally. Thus, there is a need to define new candidates to create a multivalent vaccine to increase the effectiveness of Ag2/PRA. Efforts of genomic screening using expression library immunization or bioinformatic approaches to identify new candidates have revealed at least two new protective proteins, expression library immunization antigen 1 (ELI-Ag1) and a β-1,3-glucanosyltransferase (GEL-1). In addition, previously discovered antigens such as Coccidioides-specific antigen (CSA) should be evaluated in assays of protection. While studies have yet to be completed with combinations of the current candidates, the hypothesis is that with increased numbers of candidates in a multivalent vaccine, there will be increased protection. As the genome sequences of the two Coccidioides strains which are under way are completed and annotated, the effort to find new candidates can increase to provide a complete genomic scan for immunodominant proteins. Thus, much progress has been made in the discovery of subunit vaccine candidates against Coccidioides and there are several candidates showing modest levels of protection, but for complete protection against pulmonary challenge we need to continue the search for additional candidates

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“…Further studies showed that a DC-based Coccidioides vaccine had adjuvant properties and activated protective immune responses in mice (Awasthi, 2007). Although macrophages can ingest Coccidioides; earlier studies suggested that they are not able to kill the arthroconidia (Kashkin et al, 1977;Beaman et al, 1981Beaman et al, , 1983Holmberg, 1980b, 1980a). Studies demonstrated that monocytes derived from human peripheral blood were able to kill Coccidioides (Ampel and Galgiani, 1991).…”

Section: Phagocyte Interactions With Pulmonary Fungal Pathogensmentioning

confidence: 99%

Host Immune Responses Against Pulmonary Fungal Pathogens

Wozniak¹,

Olszewski²,

Wormley³

2012

Pulmonary Infection

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infections are acquired by inhalation of fungi from contaminated soil, and severity of disease generally correlates with the amount of exposure to the pathogen. Examples of organisms that are opportunistic pulmonary fungal pathogens include Cryptococcus neoformans, Aspergillus fumigatus, Pneumocystis, and Rhizopus. C. neoformans is found ubiquitously in the soil, usually in soil contaminated with pigeon guano (Perfect and Casadevall, 2002). These fungi primarily cause disease in individuals with compromised immune systems. Most cryptococcal infections are asymptomatic, and the organism typically causes disease in immune compromised patients, such as AIDS patients, solid organ transplant patients on immune-suppressive drugs, or patients receiving chemotherapy (

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Studies on mediators of cellular immunity in experimental coccidioidomycosis

Cited by 12 publications

References 18 publications

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

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

Coccidioidomycosis: Host Response and Vaccine Development

Host Immune Responses Against Pulmonary Fungal Pathogens

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