-
Current Topics in Microbiology and... 2019Histoplasmosis, caused by the dimorphic environmental fungus Histoplasma capsulatum, is a major mycosis on the global stage. Acquisition of the fungus by mammalian hosts... (Review)
Review
Histoplasmosis, caused by the dimorphic environmental fungus Histoplasma capsulatum, is a major mycosis on the global stage. Acquisition of the fungus by mammalian hosts can be clinically silent or it can lead to life-threatening systemic disease, which can occur in immunologically intact or deficient hosts, albeit severe disease is more likely in the setting of compromised cellular immunity. H. capsulatum yeast cells are highly adapted to the mammalian host as they can effectively survive within intracellular niches in select phagocytic cells. Understanding the biological response by both the host and H. capsulatum will facilitate improved approaches to prevent and/or modify disease. This review presents our current understanding of the major pathogenic mechanisms involved in histoplasmosis.
Topics: Animals; Histoplasma; Histoplasmosis; Humans; Virulence
PubMed: 30043340
DOI: 10.1007/82_2018_114 -
Microbiology Spectrum Jun 2016Filamentous mycoses are often associated with significant morbidity and mortality. Prompt diagnosis and aggressive treatment are essential for good clinical outcomes in... (Review)
Review
Filamentous mycoses are often associated with significant morbidity and mortality. Prompt diagnosis and aggressive treatment are essential for good clinical outcomes in immunocompromised patients. The host immune response plays an essential role in determining the course of exposure to potential fungal pathogens. Depending on the effectiveness of immune response and the burden of organism exposure, fungi can either be cleared or infection can occur and progress to a potentially fatal invasive disease. Nonspecific cellular immunity (i.e., neutrophils, natural killer [NK] cells, and macrophages) combined with T-cell responses are the main immunologic mechanisms of protection. The most common potential mold pathogens include certain hyaline hyphomycetes, endemic fungi, the Mucorales, and some dematiaceous fungi. Laboratory diagnostics aimed at detecting and differentiating these organisms are crucial to helping clinicians make informed decisions about treatment. The purpose of this chapter is to provide an overview of the medically important fungal pathogens, as well as to discuss the patient characteristics, antifungal-therapy considerations, and laboratory tests used in current clinical practice for the immunocompromised host.
Topics: Antibodies, Fungal; Antifungal Agents; Aspergillus fumigatus; CD4-Positive T-Lymphocytes; Histoplasma; Humans; Immunocompromised Host; Mucorales; Mycoses
PubMed: 27337469
DOI: 10.1128/microbiolspec.DMIH2-0002-2015 -
Medical Mycology Aug 2023Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and... (Review)
Review
Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and in yeast form in infected tissues. In this narrative literature review, we summarize the occurrence of Histoplasma spp. in different species of bat tissues (n = 49) and in soil admixed with bat guano where the species of bat dwelling nearby has been identified (an additional 18 species likely infected) to provide an up-to-date summary of data. Most positive isolations are from the Americas and Caribbean, with some studies from Thailand, Malaysia, Nigeria, Slovenia, France, and Australia. We also summarize some of the early experimental work to elucidate pathogenicity, latency, immune response, and faecal excretion in bats. Given the recent recognition of the global extent of histoplasmosis, thermal dimorphism in Histoplasma spp., and global heating, additional work on understanding the complex relationship between Histoplasma and bats is desirable.
Topics: Humans; Animals; Histoplasma; Chiroptera; Histoplasmosis; Saccharomyces cerevisiae; Environment
PubMed: 37553137
DOI: 10.1093/mmy/myad080 -
Current Opinion in Microbiology Dec 2019Temperature serves as a fundamental signal in biological systems. In some microbial pathogens of humans, mammalian body temperature triggers establishment and... (Review)
Review
Temperature serves as a fundamental signal in biological systems. In some microbial pathogens of humans, mammalian body temperature triggers establishment and maintenance of a developmental program that allows the microbe to survive and thrive in the host. Histoplasma capsulatum is one of a group of fungal pathogens called thermally dimorphic fungi, all of which respond to mammalian body temperature by converting from an environmental mold form that inhabits the soil into a parasitic form that causes disease in the host. It has been known for decades that temperature is a key signal that is sufficient to trigger the switch from the soil to host form (and vice versa) in the laboratory. Recent molecular studies have identified a number of key regulators that are required to specify each of the developmental forms in response to temperature. Here we review the regulatory circuits that govern temperature-dependent dimorphism in Histoplasma.
Topics: Adaptation, Physiological; Fungal Proteins; Gene Expression Regulation, Fungal; Histoplasma; Histoplasmosis; Humans; Respiratory Tract Infections; Soil Microbiology; Temperature; Virulence
PubMed: 31739263
DOI: 10.1016/j.mib.2019.10.011 -
The New England Journal of Medicine Mar 2019
Topics: AIDS-Related Opportunistic Infections; Adult; CD4 Lymphocyte Count; Fatal Outcome; HIV Infections; Histoplasma; Histoplasmosis; Humans; Male
PubMed: 30865801
DOI: 10.1056/NEJMicm1809792 -
Applied and Environmental Microbiology Apr 2022Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves... (Review)
Review
Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves immunocompetent and immunosuppressed human and other mammalian hosts, depending on particular circumstances. Histoplasmosis infection has been documented worldwide. The infection is acquired by inhaling infective mycelial propagules of the dimorphic fungus Histoplasma capsulatum. New reports of clinical cases of histoplasmosis in extreme latitudes could be related to human social adaptations and climate changes in the world, which are creating new favorable environments for this fungus and for bats, its major natural reservoirs and dispersers. has been isolated from most continents, and it is considered a complex of cryptic species, consisting of various groups of isolates that differ genetically and correlate with a particular geographic distribution. Based on updated studies, taxonomy is adjusting to new genetic data. Here, we have suggested that has at least 14 phylogenetic species distributed worldwide and new genotypes that could be under deliberation. 's geographic radiation began in South America millions of years ago when the continents were joined and the climate was favorable. For fungal spreading, the role of bats and some birds is crucial, although other natural factors could also participate.
Topics: Animals; Chiroptera; Histoplasma; Histoplasmosis; Humans; Lung; Phylogeny
PubMed: 35262368
DOI: 10.1128/aem.02010-21 -
Frontiers in Cellular and Infection... 2020and are related thermally dimorphic fungal pathogens that cause deadly mycoses (i.e., histoplasmosis and paracoccidioidomycosis, respectively) primarily in North,... (Review)
Review
and are related thermally dimorphic fungal pathogens that cause deadly mycoses (i.e., histoplasmosis and paracoccidioidomycosis, respectively) primarily in North, Central, and South America. Mammalian infection results from inhalation of conidia and their subsequent conversion into pathogenic yeasts. Macrophages in the lung are the first line of defense, but are generally unable to clear these fungi. Instead, and yeasts survive and proliferate within the phagosomal compartment of host macrophages. Growth within macrophages requires strategies for acquisition of sufficient nutrients (e.g., carbon, nitrogen, and essential trace elements and co-factors) from the nutrient-depleted phagosomal environment. We review the transcriptomic and recent functional genetic studies that are defining how these intracellular fungal pathogens tune their metabolism to the resources available in the macrophage phagosome. In addition, recent studies have shown that the nutritional state of the macrophage phagosome is not static, but changes upon activation of adaptive immune responses. Understanding the metabolic requirements of these dimorphic pathogens as they thrive within host cells can provide novel targets for therapeutic intervention.
Topics: Animals; Histoplasma; Histoplasmosis; Macrophages; Paracoccidioides; Paracoccidioidomycosis
PubMed: 33178634
DOI: 10.3389/fcimb.2020.592259 -
Open Biology Mar 2022Exposure to fungal pathogens from the environment is inevitable and with the number of at-risk populations increasing, the prevalence of invasive fungal infection is on... (Review)
Review
Exposure to fungal pathogens from the environment is inevitable and with the number of at-risk populations increasing, the prevalence of invasive fungal infection is on the rise. An interesting group of fungal organisms known as thermally dimorphic fungi predominantly infects immunocompromised individuals. These potential pathogens are intriguing in that they survive in the environment in one form, mycelial phase, but when entering the host, they are triggered by the change in temperature to switch to a new pathogenic form. Considering the growing prevalence of infection and the need for improved diagnostic and treatment approaches, studies identifying key components of fungal recognition and the innate immune response to these pathogens will significantly contribute to our understanding of disease progression. This review focuses on key endemic dimorphic fungal pathogens that significantly contribute to disease, including , and species. We briefly describe their prevalence, route of infection and clinical presentation. Importantly, we have reviewed the major fungal cell wall components of these dimorphic fungi, the host pattern recognition receptors responsible for recognition and important innate immune responses supporting adaptive immunity and fungal clearance or the failure thereof.
Topics: Fungi; Histoplasma; Humans; Immunity, Innate
PubMed: 35259948
DOI: 10.1098/rsob.210219 -
Future Microbiology 2015Histoplasma capsulatum, an environmental fungus, is the most common endemic pulmonary mycosis in the USA. Disease is most frequently observed in immunocompromised... (Review)
Review
Histoplasma capsulatum, an environmental fungus, is the most common endemic pulmonary mycosis in the USA. Disease is most frequently observed in immunocompromised patients living in endemic areas. We present the mechanisms of fungal recognition, innate immune response and adaptive immune response that lead to protection or exacerbation of disease. Current understanding of these mechanisms is the result of a continuing dialogue between clinical observations and murine studies. Mice are a powerful model to study the immune response to H. capsulatum alone or in the presence of immunomodulatory drugs. Vigilance for histoplasmosis should be exercised with novel immunosuppressive agents that target the important immune pathways identified here.
Topics: Adaptive Immunity; Animals; Disease Models, Animal; Endemic Diseases; Histoplasma; Histoplasmosis; Humans; Immunity, Innate; Immunocompromised Host; Lung Diseases, Fungal; Mice; Opportunistic Infections; United States
PubMed: 26059620
DOI: 10.2217/fmb.15.25 -
Virulence Dec 2019is a member of a group of fungal pathogens called thermally dimorphic fungi, all of which respond to mammalian body temperature by converting from an environmental mold... (Review)
Review
is a member of a group of fungal pathogens called thermally dimorphic fungi, all of which respond to mammalian body temperature by converting from an environmental mold form into a parasitic host form that causes disease. is a primary fungal pathogen, meaning it is able to cause disease in healthy individuals. We are beginning to understand how host temperature is utilized as a key signal to facilitate growth in the parasitic yeast form and promote production of virulence factors. In recent years, multiple regulators of morphology and virulence have been identified in . Mutations in these regulators render the pathogen unable to convert to the parasitic yeast form. Additionally, several virulence factors have been characterized for their importance in survival and pathogenesis. These virulence factors and regulators can serve as molecular handles for the development of effective drugs and therapeutics to counter infection.
Topics: Animals; Body Temperature; Gene Expression Regulation, Fungal; Histoplasma; Histoplasmosis; Host-Pathogen Interactions; Humans; Mice; Mutation; Virulence; Virulence Factors
PubMed: 31560240
DOI: 10.1080/21505594.2019.1663596