Histoplasmosis

Wu-Hsieh, Betty A.; Howard, Dexter H.

doi:10.1007/978-1-4899-2400-1_9

Cited by 11 publications

(4 citation statements)

References 238 publications

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“…Disseminated disease, while rare, occurs in organs of the reticuloendothelial system and is caused via parasitism of mononuclear phagocytes. Long-term survival within macrophages even after initial disease resolution is responsible for later reactivation when host immunity is compromised (319). Features of avirulent mutants and possible virulence factors related to intracellular growth will be discussed here.…”

Section: Histoplasma Capsulatummentioning

confidence: 99%

Virulence factors of medically important fungi

1996

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Human fungal pathogens have become an increasingly important medical problem with the explosion in the number of immunocompromised patients as a result of cancer, steroid therapy, chemotherapy, and AIDS. Additionally, the globalization of travel and expansion of humankind into previously undisturbed habitats have led to the reemergence of old fungi and new exposure to previously undescribed fungi. Until recently, relatively little was known about virulence factors for the medically important fungi. With the advent of molecular genetics, rapid progress has now been made in understanding the basis of pathogenicity for organisms such as Aspergillus species and Cryptococcus neoformans. The twin technologies of genetic transformation and "knockout" deletion construction allowed for genetic tests of virulence factors in these organisms. Such knowledge will prove invaluable for the rational design of antifungal therapies. Putative virulence factors and attributes are reviewed for Aspergillus species, C. neoformans, the dimorphic fungal pathogens, and others, with a focus upon a molecular genetic approach. Candida species are excluded from coverage, having been the subject of numerous recent reviews. This growing body of knowledge about fungal pathogens and their virulence factors will significantly aid efforts to treat the serious diseases they cause.

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Section: Histoplasma Capsulatummentioning

confidence: 99%

Virulence factors of medically important fungi

1996

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“…capsulatum varies with the inoculum dose and the age and immunologic status of the host. 82 • 96 When many conidia have been inhaled, pulmonary lesions may be rapidly progressive, even in a nonimmunocompromised host and may contain large numbers of proliferating intraalveolar and interstitial yeast forms. In contrast, yeast cells are relatively sparse in mild, self-limited, chronic, progressive pulmonary infections.…”

Section: Pathologymentioning

confidence: 99%

Fungal Infections

Haque

McGinnis

2008

Dail and Hammar’s Pulmonary Pathology

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The incidence of invasive fungal infections has increased dramatically over the past two decades, mostly due to an increase in the number of immunocompromised patients. l -4 Patients who undergo chemotherapy for a variety of diseases, patients with organ transplants, and patients with the acquired immune deficiency syndrome have contributed most to the increase in fungal infections. s The actual incidence of invasive fungal infections in transplant patients ranges from 15% to 25% in bone marrow transplant recipients to 5% to 42% in solid organ transplant recipients. 6 ,7 The most frequently encountered are Aspergillus species, followed by Cryptococcus and Candida species. Fungal infections are also associated with a higher mortality than either bacterial or viral infections in these patient popUlations. This is because of the limited number of available therapies, dose-limiting toxicities of the antifungal drugs, fewer symptoms due to lack of inflammatory response, and the lack of sensitive tests to aid in the diagnosis of invasive fungal infections. I A study of patients with fungal infections admitted to a university-affiliated hospital indicated that communityacquired infections are becoming a serious problem; 67% of the 140 patients had community-acquired fungal pneumonia. 8 There is also an increase in nosocomial fungal infections.9Fungi are eukaryotic, unicellular to multicellular organisms that have chitinous cell walls, and reproduce asexually, sexually, or both ways. Fungal cells are larger and genomically more complex than bacteria. Their cell wall contains polysaccharides, proteins, and sugars, and their antigens are rich in complex polysaccharides and glycoproteins. Plasma membranes of fungi contain ergosterol, which is the primary target for antifungals such as amphotericin B. Although there are more than 1.3 million fungal species in the environment, only about 150 are known to be pathogenic to humans. For detailed taxonomy of the fungi, several texts are available. W-12 The virulence factors of fungi resemble those of bacteria, such as possession of a capsule, adhesion molecules, toxins, free radicals, etc.

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“…IFN-␥-induced antihistoplasma activity of macrophages is compromised by LCMV clone 13. Macrophages are not only the primary residence of H. capsulatum in an infected host but also the effector cells that eventually clear the infection (27). We have previously reported that murine peritoneal macrophages stimulated by IFN-␥ acquire the ability to restrict the growth of H. capsulatum (26).…”

Section: Macrophages As Target Cells For Both Lcmv Clone 13 and H Camentioning

confidence: 99%

“…Although LCMV is a noncytolytic virus, infection with it impairs the functioning of these crucial cells of the immune system. Macrophages are the primary residence of H. capsulatum in an infected host (27), and disturbance of their functioning by a virus infection would alter their ability to deal with the fungus.…”

mentioning

confidence: 99%

Impaired responsiveness to gamma interferon of macrophages infected with lymphocytic choriomeningitis virus clone 13: susceptibility to histoplasmosis

Villarete¹,

Fries²,

Kolhekar³

et al. 1995

Infect Immun

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Lymphocytic choriomeningitis virus clone 13 (LCMV clone 13), a variant isolated from the spleens of neonatally infected mice, causes persistent infections in mice infected as adults. Such persistently infected mice succumb to a normally sublethal dose of Histoplasma capsulatum, and their macrophages contain overwhelming numbers of yeast cells of the fungus. Both LCMV clone 13 and H. capsulatum yeast cells target and replicate in macrophages of the host. We sought to study the effects of LCMV clone 13 on the ability of macrophages to control growth of H. capsulatum in vitro. We show that the growth of H. capsulatum within macrophages was not directly affected by the presence of LCMV clone 13. However, macrophages containing LCMV clone 13 did not respond fully to gamma interferon (IFN-␥) stimulation. Such unresponsiveness resulted in proliferation of the fungus within macrophages cultured in the presence of IFN-␥. The addition of anti-IFN-␣/␤ antibodies to LCMV clone 13-infected macrophage cultures restored macrophage responsiveness to IFN-␥. These results indicate that production of IFN-␣/␤ by LCMV clone 13-infected macrophages antagonizes their responsiveness to IFN-␥. Such antagonism may be one of the mechanisms by means of which certain viruses cause immune suppression and susceptibility to opportunistic infections.

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Histoplasmosis

Cited by 11 publications

References 238 publications

Virulence factors of medically important fungi

Virulence factors of medically important fungi

Fungal Infections

Impaired responsiveness to gamma interferon of macrophages infected with lymphocytic choriomeningitis virus clone 13: susceptibility to histoplasmosis

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