Imaging Candida Infections in the Host

Navarathna, Dhammika H. M. L. P.; Roberts, D. A.; Munasinghe, Jeeva; Lizak, Martin J.

doi:10.1007/978-1-4939-3052-4_6

Cited by 8 publications

(5 citation statements)

References 9 publications

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“…Nos3 -/- mice had significantly lower kidney neutrophil infiltration compared with infected WT kidneys. Kidney is the major target organ in disseminated candidiasis and is responsible for mouse mortality as shown previously [24,35,36,43,47,54,55]. The decreased recruitment of innate immune cells was associated with a decreased fungal burden at the sub-acute phase in the infected Nos3 -/- kidneys.…”

Section: Discussionsupporting

confidence: 56%

“…However, excessive neutrophil accumulation in tissue during the subacute phase of the infection is deleterious, and that immunopathology can result in kidney failure and mortality [46]. The brain also a target in candida dissemination [47], but the colonization in brain was insufficient to quantify. We focused instead on assessing infiltrating leukocytes, which revealed eNOS-dependent differences in neutrophil counts that paralleled those found in infected kidneys.…”

Section: Discussionmentioning

confidence: 99%

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Endothelial nitric oxide synthase limits host immunity to control disseminated Candida albicans infections in mice

2019

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Three isoforms of nitric oxide synthase (NOS) occur in mammals. High levels of NO produced by NOS2/iNOS can protect against bacterial and parasitic infections, but the role of NOS in fungal innate immunity is less clear. Compared to wild type mice, Nos3-/- mice showed significantly higher survival of candidemia caused by Candida albicans SC5314. NOS3/eNOS is expressed by endothelial cells in the kidney, and colonization of this organ was decreased during the sub-acute stage of disseminated candidiasis. Nos3-/- mice more rapidly eliminated Candida from the renal cortex and exhibited more balanced local inflammatory reactions, with similar macrophage but less neutrophil infiltration than in infected wild type. Levels of the serum cytokines IL-9, IL-12, IL-17 and chemokines GM-CSF, MIP1α, and MIP1β were significantly elevated, and IL-15 was significantly lower in infected Nos3-/- mice. Spleens of infected Nos3-/- mice had significantly more Th2 and Th9 but not other CD4+ T cells compared with wild type. Inflammatory genes associated with leukocyte chemotaxis, IL-1 signaling, TLR signaling and Th1 and Th2 cell differentiation pathways were significantly overexpressed in infected Nos3-/- kidneys, with Nos2 being the most strongly induced. Conversely, the general NOS inhibitor NG-nitro-L-arginine methyl ester increased virulence in the mouse candidemia model, suggesting that iNOS contributes to the protective mechanism in infected Nos3-/- mice. By moderating neutrophil infiltration, the absence of eNOS may reduce the collateral damage to kidney cortex, and Th-9 CD4+ cells may enhance clearance of the infection. These data suggest that selective eNOS inhibition could mitigate candidemia by a combination of systemic and local responses that promote a more effective host immune response.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Endothelial nitric oxide synthase limits host immunity to control disseminated Candida albicans infections in mice

2019

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“…As kidneys are the main target organs of systemic candidiasis in mice ( 51 , 52 ) and our CFU data indicated marked differences in this organ between the Syk −/− or CARD9 −/− and WT chimeras, we examined the presence of fungal elements and associated leukocyte infiltrates in the kidneys using periodic acid-Schiff (PAS)-stained histological tissue sections at 2 and 30 dpi ( Fig. 6 and Fig.…”

Section: Resultsmentioning

confidence: 99%

Signaling through Syk or CARD9 Mediates Species-Specific Anti-CandidaProtection in Bone Marrow Chimeric Mice

Zajta

Csonka

Tóth

et al. 2021

mBio

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While C. albicans remains the most clinically significant Candida species, C. parapsilosis is an emerging pathogen with increased affinity to neonates. Syk/CARD9 signaling is crucial in immunity to C. albicans , but its role in in vivo responses to other pathogenic Candida species is largely unexplored.

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“…1B), suggesting that EphA2 deficiency within cells of both, the hematopoietic and stromal compartments, is required for full protection against disseminated candidiasis. Kidneys are a primary target organ of C. albicans, and invasion into the kidney medulla leads to loss of renal function and death 47,48 . Therefore, we determined the kidney fungal burden 4 days post infection.…”

Section: Epha2 Deficiency Increases Tolerance During Disseminated Candidiasismentioning

confidence: 99%

IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis

Millet

Solis

Aquilar

et al. 2021

Preprint

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During infection the host relies on pattern-recognition receptors to sense invading fungal pathogens to launch immune defense mechanisms. While fungal recognition and immune effector responses are organ and cell type specific, during disseminated candidiasis myeloid cells exacerbate collateral tissue damage. However, the complex interplay between protective antifungal immunity and immunopathology remains incompletely understood. The β-glucan receptor ephrin type-A 2 receptor (EphA2) is required to initiate mucosal inflammatory responses during oral Candida infection. Here we report that Epha2 promotes renal immunopathology during disseminated candidiasis. EphA2 deficiency leads to reduced renal inflammation and injury. Comprehensive analyses reveal that EphA2 limits IL-23 secretion in dendritic cells, while IL-23 signaling prevents ferroptotic myeloid cell death during infection. Further, ferroptosis aggravates inflammation during infection, while at the same time reducing the fungal killing capacity of macrophages. Thus, we identify ferroptotic cell death as a critical pathway of Candida-mediated renal immunopathology that opens a new avenue to tackle Candida infection and inflammation.

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Imaging Candida Infections in the Host

Cited by 8 publications

References 9 publications

Endothelial nitric oxide synthase limits host immunity to control disseminated Candida albicans infections in mice

Endothelial nitric oxide synthase limits host immunity to control disseminated Candida albicans infections in mice

Signaling through Syk or CARD9 Mediates Species-Specific Anti-CandidaProtection in Bone Marrow Chimeric Mice

IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis

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