Host–Pathogen Interactions in Coccidioidomycosis: Prognostic Clues and Opportunities for Novel Therapies

Krogstad, Paul; Johnson, Royce H.; Garcia-Lloret, M.; Heidari, Arash; Butte, Manish J.

doi:10.1016/j.clinthera.2019.08.011

Cited by 10 publications

(7 citation statements)

References 93 publications

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“…Heterozygosity for DECTIN-1 p.I223S is associated with oropharyngeal candidiasis and reduced IFN-γ production after stimulation with heat-killed Candida albicans ( 38 ). A patient homozygous for p.I223S and DCM has previously been reported ( 39 ). Furthermore, a patient with compound heterozygous DECTIN-1 variants, p.I223S and p.Y238*, had severe, treatment-refractory infection with the far less virulent mold Corynespora cassiicola ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Immunogenetics associated with severe coccidioidomycosis

Hsu¹,

Korzeniowska²,

Aguilar³

et al. 2022

JCI Insight

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Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the Southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, <1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled DCM patients and performed whole-exome sequencing. In an exploratory set of 67 DCM patients, two had haploinsufficient STAT3 mutations, while defects in b-glucan sensing and response were seen in 34/67 (50.7%) cases. Damaging CLEC7A (n=14) and PLCG2 (n=11) variants were associated with impaired production of b-glucan-stimulated TNF-a from peripheral blood mononuclear cells compared to healthy controls (P<0.005). Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were over-represented in DCM (P=0.0206, P=0.015, respectively) including CLEC7A Y238* (P=0.0105) and PLCG2 R268W (P=0.0025). A validation cohort of 111 DCM patients confirmed PLCG2 R268W (P=0.0276), CLEC7A I223S (P=0.044), and CLEC7A Y238* (P=0.0656). Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived H2O2 in transfected cells. Heterozygous DUOX1 or DUOXA1 variants which impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired b-glucan sensing or response affecting TNF-a and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.

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Section: Discussionmentioning

confidence: 99%

Immunogenetics associated with severe coccidioidomycosis

Hsu¹,

Korzeniowska²,

Aguilar³

et al. 2022

JCI Insight

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“…SARS-CoV-2 is known for creatiating CD8+ T-cell senescence that contributes to diminished cell-mediated signaling as a result of functional depletion [17]. Coccidioides infection initiates prolonged Th1 and cytotoxic T-cell response leading to impaired cytokine signaling from CD4+ Th1 and cytotoxic CD8+ T-cells, but these same CD8+ T-cells are essential for clearance and recovery in immune host defense in SARS-CoV-2 infection [16].…”

Section: Discussionmentioning

confidence: 99%

“…Host immune response to Coccidioides requires both innate and adaptive immunity, whereby tumor necrosis factor-alpha signaling regulates adaptive immunity [17]. Both CD4+ T-helper 1 and cytotoxic CD8+ T-cells coordinate humoral responses to Coccidioides.…”

Section: Discussionmentioning

confidence: 99%

Fulminant Superimposed Covid-19 Pneumonia on Coccidioidomycosis Disseminated Infection

Villafuerte¹,

Passeri²

2022

J Infect Dis Case Rep

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Coronavirus Disease 2019 (COVID-19) is a novel virus with limited data regarding co-infection with fungal pathogens. A 35-year-old, immunocompetent, male with a past medical history of pulmonary coccidioides infection presented with worsening cough, shortness of breath and hemoptysis. Patient was found positive for COVID-19 via DNA PCR and Coccidioides reactivation via antibody testing. He had received treatment for Coccidioides infection previously, but it was unknown whether he finished it due to his lack of outpatient follow-up. Specifically for COVID-19, he was started on the standard 5-day course of Remdesivir, but he experienced rapid respiratory deterioration and ultimately died.

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“…Diagnostic methods of coccidioidomycosis and clinical practice have been well reviewed [ 36 ]. Human genetic variations can contribute to high incidence rates of disseminated disease among specific populations, such as African Americans, Asian/Pacific Islanders, and Latinos, compared to European Americans [ 27 , 37 , 38 , 39 ]. Furthermore, allelic variations of immune factors of the IL-12-IFN-γ signaling, innate immune sensing, NFκB signaling, and IL-17 signaling molecules have been predicted to associate with the severity of coccidioidomycosis [ 40 , 41 ].…”

Section: Understanding the Public Health Impact Of Valley Fever Can B...mentioning

confidence: 99%

Advocating for Coccidioidomycosis to Be a Reportable Disease Nationwide in the United States and Encouraging Disease Surveillance across North and South America

Gorris

Ardon‐Dryer

Campuzano

et al. 2023

JoF

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Coccidioidomycosis (Valley fever) has been a known health threat in the United States (US) since the 1930s, though not all states are currently required to report disease cases. Texas, one of the non-reporting states, is an example of where both historical and contemporary scientific evidence define the region as endemic, but we don’t know disease incidence in the state. Mandating coccidioidomycosis as a reportable disease across more US states would increase disease awareness, improve clinical outcomes, and help antifungal drug and vaccine development. It would also increase our understanding of where the disease is endemic and the relationships between environmental conditions and disease cases. This is true for other nations in North and South America that are also likely endemic for coccidioidomycosis, especially Mexico. This commentary advocates for US state and territory epidemiologists to define coccidioidomycosis as a reportable disease and encourages disease surveillance in other endemic regions across North and South America in order to protect human health and reduce disease burden.

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Host–Pathogen Interactions in Coccidioidomycosis: Prognostic Clues and Opportunities for Novel Therapies

Cited by 10 publications

References 93 publications

Immunogenetics associated with severe coccidioidomycosis

Immunogenetics associated with severe coccidioidomycosis

Fulminant Superimposed Covid-19 Pneumonia on Coccidioidomycosis Disseminated Infection

Advocating for Coccidioidomycosis to Be a Reportable Disease Nationwide in the United States and Encouraging Disease Surveillance across North and South America

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