BALB/c and C57BL/6 Mice Differ in Polyreactive IgA Abundance, which Impacts the Generation of Antigen-Specific IgA and Microbiota Diversity.

The interrelationship between IgAs and microbiota diversity is still unclear. Here we show that BALB/c mice had higher abundance and diversity of IgAs than C57BL/6 mice and that this correlated with increased microbiota diversity. We show that polyreactive IgAs mediated the entrance of non-invasive bacteria to Peyer's patches, independently of CX3CR1(+) phagocytes. This allowed the induction of bacteria-specific IgA and the establishment of a positive feedback loop of IgA production. Cohousing of mice or fecal transplantation had little or no influence on IgA production and had only partial impact on microbiota composition. Germ-free BALB/c, but not C57BL/6, mice already had polyreactive IgAs that influenced microbiota diversity and selection after colonization. Together, these data suggest that genetic predisposition to produce polyreactive IgAs has a strong impact on the generation of antigen-specific IgAs and the selection and maintenance of microbiota diversity.

l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells.

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutin/l-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.

Evidence of a possible therapeutic role of vitamin D in a cohort of adult Caucasian vitiligo patients.

Reduced serum 25(OH)D levels have been largely reported in vitiligo, which is an autoimmune skin disorder characterized by the appearance of achromic macules. Since vitamin D can positively modulate immune function and stimulate melanogenesis in vitro, a possible role of sufficient vitamin D levels in promoting the stability of the disease and repigmentation process might be hypothesized in vitiligo. Hence, we conducted an observational study on medical records related to 101 vitiligo patients, in order to correlate baseline 25(OH)D levels with the baseline vitiligo activity and repigmentation of vitiligo macules on a 6-month follow-up. According to our results, at baseline we found that active vitiligo was significantly associated with 25(OH)D deficiency (≤20 ng/mL) (P = 0.036) or insufficiency (21-29 ng/mL) (P = 0.041), while stable disease was significantly associated with sufficient 25(OH)D levels (30-100 ng/mL) (P = 0.043). After 6 months, vitiligo patients with sufficient 25(OH)D levels (30-100 ng/mL) achieved a significantly higher degree of repigmentation. In conclusion, our study provides a novel evidence of a significant positive association of sufficient 25(OH)D levels with the stability of the disease and a satisfactory repigmentation process in Caucasian adult vitiligo patients and strengthen the need to assess vitamin D status in vitiligo. The correlation between sufficient vitamin D levels and a satisfactory course of the disease opens the way for future randomized controlled trials assessing a possible beneficial role of vitamin D supplementation on vitiligo.

ROS-challenged keratinocytes as a new model for oxidative stress-mediated skin diseases.

In the current study, the effects of the reactive oxygen species (ROS) generator 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) on extracellular and intracellular ROS production in human keratinocytes (HACAT) were studied. AAPH is a water-soluble compound able to generate ROS at known and constant rates at 37°C. The short treatment (2 h) with AAPH brought a significant dose-dependent increase in NADPH oxidase activity in intact keratinocytes. The long-term treatment (24 h) with AAPH led to a persistent increase in NADPH oxidase activity for up to 48 hour following the AAPH removal from cell incubation medium. ROS and nitric oxide levels, lipoperoxidation, intracellular calcium, mitochondrial superoxide production, and membrane potential were significantly modified in AAPH-treated HACAT. Superoxide dismutase (SOD) and/or catalase addition to HACAT revealed that untreated keratinocytes produce mostly superoxide anion (O 2- ), while AAPH-treated keratinocytes overproduce hydrogen peroxide (H 2 O 2 ) in extracellular medium. H 2 O 2 is particularly stable and plays important roles in several cell signaling pathways. Taken together, our findings suggest a cost-effective and easily reproducible in vitro model of stressed human keratinocytes releasing significantly elevated ROS amounts in extracellular medium with respect to control keratinocytes. The possible application of the proposed model for keratinocytes-melanocytes cross-talk studies is also suggested. The model of AAPH-stressed human keratinocytes described here can represent a useful tool for redox cross-talk studies between keratinocytes and other skin cell types, and applied for researches regarding skin pathologies associated with oxidative stress.

Fungal Chitin Induces Trained Immunity in Human Monocytes during Cross-talk of the Host with Saccharomyces cerevisiae.

The immune system is essential to maintain the mutualistic homeostatic interaction between the host and its micro- and mycobiota. Living as a commensal,Saccharomyces cerevisiaecould potentially shape the immune response in a significant way. We observed thatS. cerevisiaecells induce trained immunity in monocytes in a strain-dependent manner through enhanced TNFα and IL-6 production upon secondary stimulation with TLR ligands, as well as bacterial and fungal commensals. Differential chitin content accounts for the differences in training properties observed among strains, driving induction of trained immunity by increasing cytokine production and direct antimicrobial activity bothin vitroandin vivo These chitin-induced protective properties are intimately associated with its internalization, identifying a critical role of phagosome acidification to facilitate microbial digestion. This study reveals how commensal and passenger microorganisms could be important in promoting health and preventing mucosal diseases by modulating host defense toward pathogens and thus influencing the host microbiota-immune system interactions.

No Association between Vitiligo and Obesity: A Case-Control Study.

OBJECTIVE: The purpose of this study was to investigate the relationship between vitiligo and body mass index (BMI) to assess the possible association between vitiligo and obesity. SUBJECTS AND METHODS: This was a case-control study on a total of 400 participants, i.e., 200 patients with vitiligo and 200 healthy volunteers. Medical assessments were performed by dermatologists using the modified Vitiligo European Task Force form. The height and weight of all of the participants were measured and used to calculate the BMI. Data were analyzed using multivariate logistic regression models. Adjustment for age and gender was carried out preliminarily in the case-control analysis, whereas a forward stepwise selection algorithm was used to assess which independent factors were associated with a BMI ≥30 or a BMI ≤18.5. RESULTS: Comparison of the vitiligo and control groups revealed the absence of a significant association. The multivariate analysis of factors associated with a high BMI (≥30) in vitiligo patients showed a significant association between a high BMI and a sudden onset of vitiligo (p = 0.021; OR = 3.83; 95% CI 1.22-11.99) and the presence of inflammation and pruritus (p = 0.031; OR = 3.26; 95% CI 1.11-9.57). No significant association was observed in the analysis of factors associated with a low BMI (≤18.5) in vitiligo patients. CONCLUSION: In this study, vitiligo did not appear to be associated with a high BMI; obesity might not be a risk factor for vitiligo, in contrast to most autoimmune diseases which are significantly associated with obesity.

IL-37 inhibits inflammasome activation and disease severity in murine aspergillosis.

Since IL-37 transgenic mice possesses broad anti-inflammatory properties, we assessed whether recombinant IL-37 affects inflammation in a murine model of invasive pulmonary aspergillosis. Recombinant human IL-37 was injected intraperitoneally into mice prior to infection and the effects on lung inflammation and inflammasome activation were evaluated. IL-37 markedly reduced NLRP3-dependent neutrophil recruitment and steady state mRNA levels of IL-1ß production and mitigated lung inflammation and damage in a relevant clinical model, namely aspergillosis in mice with cystic fibrosis. The anti-inflammatory activity of IL-37 requires the IL-1 family decoy receptor TIR-8/SIGIRR. Thus, by preventing activation of the NLRP3 inflammasome and reducing IL-1ß secretion, IL-37 functions as a broad spectrum inhibitor of the innate response to infection-mediated inflammation, and could be considered to be therapeutic in reducing the pulmonary damage due to non-resolving Aspergillus infection and disease.

A polysaccharide virulence factor from Aspergillus fumigatus elicits anti-inflammatory effects through induction of Interleukin-1 receptor antagonist.

The galactosaminogalactan (GAG) is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated. In the present study we used in vitro PBMC stimulation assays to demonstrate, that GAG inhibits proinflammatory T-helper (Th)1 and Th17 cytokine production in human PBMCs by inducing Interleukin-1 receptor antagonist (IL-1Ra), a potent anti-inflammatory cytokine that blocks IL-1 signalling. GAG cannot suppress human T-helper cytokine production in the presence of neutralizing antibodies against IL-1Ra. In a mouse model of invasive aspergillosis, GAG induces IL-1Ra in vivo, and the increased susceptibility to invasive aspergillosis in the presence of GAG in wild type mice is not observed in mice deficient for IL-1Ra. Additionally, we demonstrate that the capacity of GAG to induce IL-1Ra could also be used for treatment of inflammatory diseases, as GAG was able to reduce severity of an experimental model of allergic aspergillosis, and in a murine DSS-induced colitis model. In the setting of invasive aspergillosis, GAG has a significant immunomodulatory function by inducing IL-1Ra and notably IL-1Ra knockout mice are completely protected to invasive pulmonary aspergillosis. This opens new treatment strategies that target IL-1Ra in the setting of acute invasive fungal infection. However, the observation that GAG can also protect mice from allergy and colitis makes GAG or a derivative structure of GAG a potential treatment compound for IL-1 driven inflammatory diseases.

PTX3 binds MD-2 and promotes TRIF-dependent immune protection in aspergillosis.

The long pentraxin 3 (PTX3) modulates different effector pathways involved in innate resistance to Aspergillus fumigatus, including complement activation or promotion of phagocytosis by interacting with FcγRs. However, whether and how TLRs modulate PTX3 mediates antifungal resistance is not known. In this study, we demonstrate that PTX3 binds myeloid differentiation protein 2 (MD-2) in vitro and exerts its protective antifungal activity in vivo through TLR4/MD-2-mediated signaling. Similar to Tlr4(-/-) mice, Md2(-/-) mice displayed high susceptibility to pulmonary aspergillosis, a phenotype associated with a proinflammatory cytokine profile and impaired antifungal activity of polymorphonuclear neutrophils. Treating Md2(-/-) mice with PTX3 failed to confer immune protection against the fungus, whereas adoptive transfer of MD-2-competent polymorphonuclear neutrophils restored it. Mechanistically, engagement of MD-2 by PTX3-opsonized Aspergillus conidia activated the TLR4/Toll/IL-1R domain-containing adapter inducing IFN-ß-dependent signaling pathway converging on IL-10. Thus, we have identified a novel receptor mechanism, involving the TLR4/MD-2/Toll/IL-1R domain-containing adapter inducing IFN-ß-mediated signaling, whereby PTX3 elicits antifungal resistance with limited immunopathology in A. fumigatus infection.

Efficacy of Rhodamine Light in the Treatment of Superficial Vascular Lesions of the Face.

OBJECTIVE: The aim of this work was to verify the usefulness and efficacy of treating superficial vascular lesions of the face using rhodamine intense pulsed light (r-IPL). SUBJECTS AND METHODS: Fifty patients suffering from telangiectasias of the face were enrolled and subsequently treated 4 times (every 20 days) with a new intensified r-IPL system optimized at the same wavelength as the dye laser (595 nm). The outcome was assessed using photographs, and clinical evaluations were made based on the percentage of fading of the erythema and telangiectasias in the lesions after treatment. RESULTS: Marked clinical improvements (70-100%) were observed in 31 (62%) patients after the second session of r-IPL, while 46 (92%) showed a marked improvement after the fourth session. No patients had to resort to topical or systemic drugs. CONCLUSION: r-IPL was effective in treating superficial vascular lesions, no side effects were observed and the patients readily accepted the treatment. Hence, r-IPL could be promising for the treatment of superficial vascular lesions of the face. Future study would be necessary to confirm the long-term efficacy of this technique.

Hair and Scalp Disorders in a Tuscan Pediatric Dermatological Outpatient Clinic: A Clinical and Epidemiological Evaluation.

OBJECTIVES: The aim of this study was to evaluate the clinical and epidemiological profile of hair and scalp disorders in children referred to the Pediatric Dermatology Outpatient Clinic. MATERIALS AND METHODS: We performed a retrospective study of children with hair loss problems or scalp diseases who turned to the Pediatric Dermatology Service, Anna Meyer Pediatric Hospital, Florence, Italy, from January 1, 2009, to December 31, 2009. Demographics, personal and familial medical history, laboratory tests, clinical examination, final diagnosis and therapeutic interventions were obtained from the manual chart review. RESULTS: Of the 2,640 children who had access to the Pediatric Dermatology Service, 190 (7.19%) had a hair or scalp disorder. Among the 190 children, 60 (31.57%) presented with nonscarring alopecia, 56 (29.47%) had benign neoplasias, hamartomas or vascular malformations of the scalp, 51 (26.84%) had scalp inflammatory diseases, 14 (7.36%) had scarring alopecia, 5 (2.63%) had infections and 2 (1.05%) had infestation of the scalp. A case of constitutional hypertrichosis (0.52%) and also a case (0.52%) of lamellar ichthyosis were diagnosed. CONCLUSIONS: Our results underline that hair and scalp diseases represent an important percentage of admittances to a dermatological pediatric outpatient clinic. The variety and complexity of the diseases observed in this study included diseases commonly found also in adulthood.

Microbiota control of a tryptophan-AhR pathway in disease tolerance to fungi.

An increased understanding of the importance of microbiota in shaping the host's immune and metabolic activities has rendered fungal interactions with their hosts more complex than previously appreciated. The aryl hydrocarbon receptor (AhR) has a pivotal role in connecting tryptophan catabolism by microbial communities and the host's own pathway of tryptophan metabolite production with the orchestration of T-cell function. AhR activation by a Lactobacillus-derived AhR ligand leads to the production of IL-22 to the benefit of mucosal defense mechanisms, an activity upregulated in the absence of the host tryptophan catabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO1), which is required for protection from fungal diseases ("disease tolerance"). As AhR activation in turn leads to the activation-in a feedback fashion-of IDO1, the regulatory loop involving AhR and IDO1 may have driven the coevolution of commensal fungi with the mammalian immune system and the microbiota, to the benefit of host survival and fungal commensalism. This review will discuss the essential help the microbiota provides in controlling the balance between the dual nature of the fungal-host relationship, namely, commensalism vs. infection.

IL-22 and IDO1 affect immunity and tolerance to murine and human vaginal candidiasis.

The ability to tolerate Candida albicans, a human commensal of the gastrointestinal tract and vagina, implicates that host defense mechanisms of resistance and tolerance cooperate to limit fungal burden and inflammation at the different body sites. We evaluated resistance and tolerance to the fungus in experimental and human vulvovaginal candidiasis (VVC) as well as in recurrent VVC (RVVC). Resistance and tolerance mechanisms were both activated in murine VVC, involving IL-22 and IL-10-producing regulatory T cells, respectively, with a major contribution by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). IDO1 was responsible for the production of tolerogenic kynurenines, such that replacement therapy with kynurenines restored immunoprotection to VVC. In humans, two functional genetic variants in IL22 and IDO1 genes were found to be associated with heightened resistance to RVVC, and they correlated with increased local expression of IL-22, IDO1 and kynurenines. Thus, IL-22 and IDO1 are crucial in balancing resistance with tolerance to Candida, their deficiencies are risk factors for RVVC, and targeting tolerance via therapeutic kynurenines may benefit patients with RVVC.

Evaluation of an oral supplement containing Phyllanthus emblica fruit extracts, vitamin E, and carotenoids in vitiligo treatment.

Phyllanthus emblica, vitamin E, and caroteinods are compounds showing antioxidative, anti-inflammatory, and repigmenting effects, whose role in vitiligo treatment has not been evaluated so far. Sixty-five subjects (group A) were treated with one tablet of an oral supplement containing P. emblica (100 mg), vitamin E (10 mg), and carotenoids (4.7 mg) three times/day for 6 months and compared with a control group (group B, 65 patients), which instead was not treated with antioxidants. Both groups were simultaneously treated with a comparable topical therapy and/or phototherapy. After a 6 months follow-up, a significantly higher number of patients in group A had a mild repigmentation on the head/neck regions (p = 0.019) and on the trunk (trend, p = 0.051). The number of patients who presented no repigmentation in head/neck, trunk, upper, and lower limbs was significantly higher in group B (respectively, p = 0.009, p = 0.001, p = 0.001, p = 0.025). Moreover, group B patients showed higher signs of inflammation (p = 0.002), a more rapid growth of the lesions (p = 0.039), a higher percentage of worsening disease (p = 0.003), and more erythema (p = 0.059), whereas group A patients showed a higher percentage of steady disease (p = 0.065). Our results suggest that the supplement with antioxidants in patients with vitiligo might represent a valuable instrument to increase the effectiveness of other vitiligo treatments. [Correction added after online publication 06-Oct-2014: the dosages of vitamin E and carotenoids have been updated.].

Correlation of Serum Thyroid Hormones Autoantibodies with Self-Reported Exposure to Thyroid Disruptors in a Group of Nonsegmental Vitiligo Patients.

Vitiligo is a pigmentary disorder strongly associated with autoimmune thyroid disorders (ATD). Thyroid hormones antibodies (THAb) directed toward thyroxine (T3) and triiodothyronine (T4) (T3- and T4-Ab) are rare in the general population but are increased in individuals wit ATD and extrathyroid autoimmune disorders. Because it is known that alcohol, smoke, iodine, and some thyroid disruptors can elicit the appearance of ATD, the aim of our study was to evaluate possible correlation between T3- and T4-Ab expression and past toxic exposures in vitiligo patients. Seventy vitiligo patients were examined and self-reported exposure to thyroid disruptors (4,4'-isopropylidenediphenol, perchlorates, polychlorinated biphenyls (PCBs), hexachlorobenzene, resorcinol, dichlorodiphenyltrichloroethane, alachlor/amitriole, nitrate, thiocyanate, soy isoflavones), iodine intake, smoke, and alcohol consumption were investigated through standardized questionnaires. Immunoglobulin (Ig)M-T3-Ab, IgG-T3-Ab, IgM-T4-Ab,and IgG-T4-Ab were dosed by a radioimmunoprecipitation technique. Seventy-seven (95.7 %) patients had at least one type of THAb. Most of them had contemporarily both T3- and T4-Ab (50/70). We found a significant association between PCBs and T4-IgG-Ab (P = 0.039) and between food intake containing nitrate, thiocyanate, and soy isoflavones with (IgM + IgG)-T3-Ab (P = 0.041). Our study underlines a possible influence of diet and environment in vitiligo patients in eliciting THAb. Therefore, in the event of a positive exposure to thyroid disruptors, an evaluation of thyroid function might be useful to early detect possible associated thyroid autoantibodies such as THAb.

An immunomodulatory activity of micafungin in preclinical aspergillosis.

OBJECTIVES: Micafungin inhibits 1,3-ß-D-glucan synthase and interferes with fungal cell wall synthesis. Clinically, micafungin has been shown to be efficacious for the treatment of invasive fungal infections. However, little is known about the immunomodulatory activity of micafungin in these infections. METHODS: We evaluated the immunomodulatory activity of escalating doses of micafungin in murine and human polymorphonuclear neutrophils (PMNs) in vitro and in vivo in different preclinical models of invasive aspergillosis, including mice deficient for selected innate immune receptors. RESULTS: Micafungin was able to regulate PMN cytokine response to Aspergillus fumigatus conidia by decreasing the expression of tumour necrosis factor-α and increasing that of interleukin-10 (IL-10). In vivo, the therapeutic efficacy of micafungin was strictly dose-dependent, with the maximum activity observed at the highest dose, concomitant with reduced inflammatory pathology. The anti-inflammatory activity of micafungin required IL-10 and occurred through signalling via the TLR2/dectin-1 and TLR3/TRIF pathways. CONCLUSION: Together, these findings suggest that the therapeutic efficacy of micafungin in aspergillosis is orchestrated by the activation of innate immune receptors affecting the inflammatory/anti-inflammatory balance during infection.

TLR3 essentially promotes protective class I-restricted memory CD8⁺ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients.

Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8⁺ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8⁺ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4⁺ and CD8⁺ T cells mediate protective memory responses to the fungus contingent on the nature of the fungal vaccine. Mechanistically, class I MHC-restricted, CD8⁺ memory T cells were activated through TLR3 sensing of fungal RNA by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated with susceptibility to aspergillosis and concomitant failure to activate memory-protective CD8⁺ T cells both in mice and in patients receiving stem-cell transplantations. Therefore, TLR3 essentially promotes antifungal memory CD8⁺ T-cell responses and its deficiency is a novel susceptibility factor for aspergillosis in high-risk patients.

Dermatosis Papulosa Nigra and 10,600-nm CO2 laser, a good choice.

Dermatosis Papulosa Nigra (DPN) is a common skin condition observed in black people and considered a benign epithelial tumor, and more specifically, a particular topographic form of seborrheic keratosis. We treated five female patients affected by DPN with 10,600-nm CO2 laser. We propose the 10,600-nm CO2 laser as a valid therapeutic option in patients affected by DPN, since the treatment is well tolerated, causes no major side effects, and is effective and long lasting.

ß-adrenoceptors are upregulated in human melanoma and their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell lines.

Recent studies sight ß-adrenergic receptor (AR) antagonists as novel therapeutic agents for melanoma, as they may reduce disease progression. Here within, we evaluated the expression of ß-ARs in a series of human cutaneous melanocytic lesions, and studied the effect of their endogenous agonists, norepinephrine (NE) and epinephrine (E), on primary and metastatic human melanoma cell lines. Using immunohistochemistry, we found that both ß1- and ß2-ARs are expressed in tissues from benign melanocytic naevi, atypical naevi and malignant melanomas and that expression was significantly higher in malignant tumours. Melanoma cell lines (human A375 primary melanoma cell line and human Hs29-4T metastatic melanoma cell lines) also expressed ß1- and ß2-ARs by measuring transcripts and proteins. NE or E increased metalloprotease-dependent motility, released interleukin-6 and 8 (IL-6, IL-8) and vascular endothelial growth factor (VEGF). These effects of catecholamines were inhibited by the unselective ß-AR antagonist propranolol. The role of soluble factors elicited by catecholamines seemed pleiotropic as VEGF synergized with NE increased melanoma invasiveness through 3D barriers, while IL-6 participated in stromal fibroblast activation towards a myofibroblastic phenotype. Our results indicate that NE and E produce in vitro via ß-ARs activation a number of biological responses that may exert a pro-tumorigenic effect in melanoma cell lines. The observation that ß-ARs are upregulated in malignant melanoma tissues support the hypothesis that circulating catecholamines NE and E, by activating their receptors, favour melanoma progression in vivo.

Galactosaminogalactan, a new immunosuppressive polysaccharide of Aspergillus fumigatus.

A new polysaccharide secreted by the human opportunistic fungal pathogen Aspergillus fumigatus has been characterized. Carbohydrate analysis using specific chemical degradations, mass spectrometry, ¹H and ¹³C nuclear magnetic resonance showed that this polysaccharide is a linear heterogeneous galactosaminogalactan composed of α1-4 linked galactose and α1-4 linked N-acetylgalactosamine residues where both monosacharides are randomly distributed and where the percentage of galactose per chain varied from 15 to 60%. This polysaccharide is antigenic and is recognized by a majority of the human population irrespectively of the occurrence of an Aspergillus infection. GalNAc oligosaccharides are an essential epitope of the galactosaminogalactan that explains the universal antibody reaction due to cross reactivity with other antigenic molecules containing GalNAc stretches such as the N-glycans of Campylobacter jejuni. The galactosaminogalactan has no protective effect during Aspergillus infections. Most importantly, the polysaccharide promotes fungal development in immunocompetent mice due to its immunosuppressive activity associated with disminished neutrophil infiltrates.