Noninhibitory binding of human interleukin-2-activated natural killer cells to the germ tube forms of Candida albicans

Arancia, Giuseppe; Molinari, Agnese; Crateri, Pasqualina; Stringaro, Annarita; Ramoni, Carlo; Dupuis, Maria Luisa; Gómez, Marı́a; Torosantucci, Antonella; Cassone, A

doi:10.1128/iai.63.1.280-288.1995

Cited by 28 publications

(7 citation statements)

References 41 publications

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“…This may argue for the presence of another pump (we demonstrated CDR gene overexpression) or a completely different mechanism affecting both fluconazole resistance and virulence, as was demonstrated in these isolates (12). Changes in ligands for phagocyte receptors, potential to elicit cytokine production, morphotype, phospholipases, or other factors could account for altered virulence of some isolates (2,3,8,10,13).…”

Section: Discussionmentioning

confidence: 60%

Fluconazole versus Candida albicans : A Complex Relationship

Graybill

Montalbo

Kirkpatrick

et al. 1998

Antimicrob Agents Chemother

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A murine model of systemic candidiasis was used to assess the virulence of serial Candida albicans strains for which fluconazole MICs were increasing. Serial isolates from five patients with 17 episodes of oropharyngeal candidiasis were evaluated. The MICs for these isolates exhibited at least an eightfold progressive increase from susceptible (MIC < 8 μg/ml; range, 0.25 to 4 μg/ml) to resistant (MIC ≥ 16 μg/ml; range, 16 to ≥128 μg/ml). Virulence of the serial isolates from three of five patients showed a more than fivefold progressive decrease in the dose accounting for 50% mortality and was associated with development of fluconazole resistance. Low doses of fluconazole prolonged survival of mice infected with susceptible yeasts but failed to prolong survival following challenge with a resistant strain. In addition, a decreased burden of renal infection was noted in mice challenged with two of the three resistant strains. This was consistent with reduced virulence. Fluconazole did not further decrease the level of infection. In the isolates with a decrease in virulence, two exhibited overexpression of CDR, which encodes an ABC drug efflux pump. In contrast, serial isolates from the remaining two patients with the development of resistance did not demonstrate a change in virulence and fluconazole remained effective in prolonging survival, although significantly higher doses of fluconazole were required for efficacy. Resistant isolates from both of these patients exhibited overexpression of MDR. This study demonstrates that decreased virulence of serial C. albicans isolates is associated with increasing fluconazole MICs in some cases but not in others and shows that these low-virulence strains may not consistently cause infection.

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Section: Discussionmentioning

confidence: 60%

Fluconazole versus Candida albicans : A Complex Relationship

Graybill

Montalbo

Kirkpatrick

et al. 1998

Antimicrob Agents Chemother

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“…Additionally, NK-depleted mice with severe combined immunodeficiency did not show enhanced susceptibility to systemic C. albicans infection (45). Although NK cells lack direct candidacidal capacity (46,47), these cells can activate phagocytes by secreting IFNγ (48,49). Interestingly, C. albicans suppresses NK cell function via induction of myeloid-derived suppressor cells, thus questioning the functional stability of NK cells in this system (50,51).…”

Section: Discussionmentioning

confidence: 99%

Unexpected kidney-restricted role for IL-17 receptor signaling in defense against systemic Candida albicans infection

Ramani¹,

Jawale²,

Verma³

et al. 2018

JCI Insight

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Kidney injury is a frequent outcome in patients with disseminated Candida albicans fungal infections. IL-17 receptor (IL-17R) signaling is critical for renal protection against disseminated candidiasis, but the identity and function of IL-17-responsive cells in mediating renal defense remains an active area of debate. Using BM chimeras, we found that IL-17R signaling is required only in nonhematopoietic cells for immunity to systemic C. albicans infection. Since renal tubular epithelial cells (RTEC) are highly responsive to IL-17 in vitro, we hypothesized that RTEC might be the dominant target of IL-17 activity in the infected kidney. We generated mice with a conditional deletion of IL-17 receptor A (Il17ra) in RTEC (Il17raΔRTEC). Strikingly, Il17raΔRTEC mice showed enhanced kidney damage and early mortality following systemic infection, very similar to Il17ra-/- animals. Increased susceptibility to candidiasis in Il17raΔRTEC mice was associated with diminished activation of the renal protective Kallikrein-kinin system (KKS), resulting in reduced apoptosis of kidney-resident cells during hyphal invasion. Moreover, protection was restored by treatment with bradykinin, the major end-product of KKS activation, which was mediated dominantly via bradykinin receptor b1. These data show that IL-17R signaling in RTEC is necessary and likely sufficient for IL-17-mediated renal defense against fatal systemic C. albicans infection.

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“…Nevertheless, macrophages are considered to be important as a mechanism of CD4 Th1‐type defenses and PMNL certainly infiltrate into mucosal tissues. Natural killer cells, on the other hand, are not considered to be effective against Candida (Djeu and Blanchard, 1987; Arancia et al , 1995). Despite the potential role for PMNL against Candida at mucosal sites, studies in animals have not revealed a role for them at the vaginal mucosa.…”

Section: Host Defense Mechanisms Against C Albicansmentioning

confidence: 99%

Immunity to Candida

2002

Oral Diseases

136

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Candida species are commensal fungal organisms as well as opportunistic pathogens of mucosal tissues. From the commensal relationship, most healthy individuals have demonstrable Candida-specific immunity. In immunocompromised persons, however, fungal infections caused primarily by C. albicans often occur. In HIV disease, up to 90% of HIV+ persons will have a symptomatic episode of oropharyngeal candidiasis (OPC) sometime during progression to AIDS, many of which become recurrent. In contrast, vulvovaginal candidiasis (VVC) and systemic Candida infections (candidaemia) are much less common during HIV disease, indicating the diversity and compartmentalization of the host response to Candida. Both innate resistance and acquired immunity play some role in maintaining C. albicans in the commensal state and protecting the systemic circulation. Polymorphonuclear leukocytes (PMNL) are critical for protection against systemic infections, whereas cell-mediated immunity (CMI) by Th1-type CD4+ T-cells is important for protection against mucosal infections. However, there is a discordant role for CMI at the vaginal versus oral mucosa, whereas little to no role for local or systemic CMI is evident at the vaginal mucosa. In contrast, there is a strong correlation between reduced blood CD4+ cells and the incidence of OPC, but it remains unclear whether systemic or local CMI is more important. Evaluation of systemic CMI in a cohort of HIV+ individuals with and without mucosal candidiasis revealed that Candida-specific CMI is not different between HIV+ persons with OPC or VVC and HIV- persons. Thus, the correlation of reduced CD4+ cell numbers to OPC may be explained by the requirement for a threshold number of systemic CD4+ cells to protect the oral mucosa together with the status of local immunity. Indeed, HIV+ persons with and without OPC had a Th2-type salivary cytokine profile suggestive of susceptibility to Candida infection compared with a protective Th0/Th1-type profile in HIV- persons. Candida-specific antibodies, although present, are controversial relative to a role in protection or eradication of infection. While studies of mucosal innate resistance are limited, we recently found that epithelial cells from saliva and vaginal lavages of healthy individuals inhibit the growth of Candida in vitro. This epithelial cell anti-Candida activity requires cell contact by viable cells with no role for soluble factors, including saliva. Interestingly, oral epithelial cells from HIV+ persons with OPC had significantly reduced activity, indicating some protective role for the epithelial cells. Taken together, these data suggest that immunity to Candida is site-specific, compartmentalized and involves innate and/or acquired mechanisms from systemic and/or local sources.

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Noninhibitory binding of human interleukin-2-activated natural killer cells to the germ tube forms of Candida albicans

Cited by 28 publications

References 41 publications

Fluconazole versus Candida albicans : A Complex Relationship

Fluconazole versus Candida albicans : A Complex Relationship

Unexpected kidney-restricted role for IL-17 receptor signaling in defense against systemic Candida albicans infection

Immunity to Candida

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