Lecture 21: Endemic Mycoses

Endemic Mycoses Immune Response

PRRs on phagocytes bind fungal PAMPs → Phagocytosis & induction of immune responses

Tissue form survives and replicates inside of phagocytes – are facultative intracellular pathogens of phagocytes

Infection can lead to granulomatous inflammation

Activation of T cells:

Effector Th1 cytokines stimulate a strong CMI response → Resolution in healthy hosts

Th17 cytokines will recruit neutrophils and promote epithelial repair

Antibodies produced participate in clearance

Coccidioides

Histoplasma

Blastomyces

Paracoccidioides

Coccidioidomycosis

Valley Fever

Coccidioides immitis (CA) and Coccidioides posadasii (outside CA)

Dimorphic fungi:

Mold in the environment; hyphae with arthroconidia and mycelia in culture at room temperature

Spherules in the host, containing endospores

Found in lungs; can disseminate to other tissues

Coccidioides

Coccidioides

Erythema Nodosum

Can be triggered by infection with Coccidioides

Often involves lower extremities

Type IV hypersensitivity response to fungal antigens; appears 1-3 weeks after initial respiratory symptoms

Red, tender subcutaneous nodules

Serves as a good prognostic indicator – patient is exhibiting a strong CMI response

Organisms are not present in the lesions

Erythema Multiforme

Can be triggered by infection with Coccidioides

Likely a combination of hypersensitivity responses: Type III = immune complex-mediated & Type IV = delayed-type

Epithelial damage is often due to CMI responses, with a predominance of CD8 T cells and macrophages

Deposits of complement C3, IgM, and fibrin around dermal blood vessels

Red, target-like lesions

Lesions often appear within ~48 hours after initial respiratory symptoms

Higher risk for Coccidioidomycosis Dissemination

Immunocompromising condition, pregnancy, and African-American race or Filipino ethnicity

Histoplasmosis

Histoplasmosis

Histoplasma capsulatum var. capsulatum

Ohio, Missouri, & Mississippi River Valleys

Soil-based fungus with bird or bat droppings

Mold in the environment and in

culture at room temperature; hyphae with microconidia & tuberculate macroconidia

Yeast form in the host and

culture at 37C

Narrow-based budding yeast often within phagocytes

Blastomycosis

Blastomycosis

Blastomycosis

Blastomyces dermatitidis

Midwestern, south-central, and southeastern states

Soil-based fungus

Fungus resides in moist soil & decomposing organic material

Mold in the environment and in culture at room temperature; branching hyphae with conidia on slender terminal or lateral conidiophores

Yeast form in the host & culture at 37 C

Thick-walled, broad-based budding yeast

Paracoccidioidomycosis

Paracoccidioidomycosis

Paracoccidioides brasiliensis complex and P. lutzii

Central and South America (esp Brazil)

Infects lungs & skin

Likely soil-based fungi; agricultural areas

Mold in the environment & in culture at room temperature; hyphae with conidia

Yeast form in the host and culture at 37 C

Large, multiple budding yeast cells; buds attached by a narrow connection – “mariner’s or ship-captain’s wheel” appearance

Triazoles

Inhibit ergosterol synthesis

Amphotericin B

Aggregates with ergosterol, forming membrane pores