Background Talaromycosis caused by Talaromyces marneffei infection is a fatal systemic mycosis in immunosuppressed individuals, such as patients with AIDS. Cytokines and immunocytes play a central role against fungus infection. However, how the host immune system responds to infection and treatment has not been reported to date. Methods Forty-one Talaromyces marneffei coinfected AIDS patients were followed up, their immunocytes and cytokine profiles were obtained at different antifungal treatment stages, and data on clinical features and laboratory examinations were collected. Correlation analysis was used to identify factors associated with host immunity against Talaromyces marneffei infection in AIDS patients. Results Common diseases and conditions of these 41 patients were lymphadenopathy, hepatomegaly, and splenomegaly. CD4+ T cells were extremely low in all of them. Moreover, significant increases of proinflammatory cytokines (IL-12, IL-17A, TNF-α, IFN-γ, IL-18, and IL-1β), anti-inflammatory cytokines (IL-10), and chemokines (IP-10) were observed in talaromycosis before treatment (P < .05), comparing to both AIDS patients and healthy controls. The cytokines IL-6, IL-8, TNF-α, IL-18, IL-17A, IL-7, IP-10, and IL-1β reached peak levels 3 days after initial antifungal therapy, and then gradually decreased. The symptoms of the patients gradually decreased. Furthermore, patients who died showed the highest levels of IL-6, TNF-α, IL-8, IL-1β, and IP-10, which were 1.4- to 164-fold higher than in surviving patients. Conclusions Our findings indicate that innate immune-cell-derived cytokines are critical for host defense against AIDS-associated Talaromyces marneffei infection; furthermore, excessive inflammatory cytokines are associated with poor outcomes.

Sweet's syndrome and eosinophilic folliculitis are aseptic inflammatory dermatitis mainly because of infiltrated neutrophils and eosinophils on skin, respectively. These diseases rarely overlap or coexist in the same patient, especially co-occur in HIV infected patient. Here, we report a rare case of an AIDS patient who developed eosinophilic folliculitis and Sweet's syndrome within 1 month of initial antiretroviral therapy, presumably due to immune reconstitution inflammatory syndrome. The CD4 + T cell counts increased dramatically from 70 to 249 cells/µL within a period of 1 month. Interestingly, the patient was rapidly and strikingly responsive to thalidomide, which has anti-inflammatory, immune regulation, inhibition of neutrophil chemotaxis etc. Moreover, we focused our attention on discussing the clinical, pathological, and possible pathogenic aspects of the rare overlap of HIV complicated with neutrophilic and eosinophilic dermatosis.

Background: The clinical and laboratory characteristics of AIDS-associated Talaromyces marneffei infection, a rare but a fatal mycosis disease of the central nervous system, remain unclear. Case presentation: Herein, we conducted a retrospective study of ten AIDS patients with cerebrospinal fluid culture-confirmed central nervous system infection caused by Talaromyces marneffei. All 10 patients were promptly treated with antifungal treatment for a prolonged duration and early antiviral therapy (ART). Among them, seven patients were farmers. Nine patients were discharged after full recovery, while one patient died during hospitalization, resulting in a mortality rate of 10%. All patients initially presented symptoms and signs of an increase in intracranial pressure, mainly manifesting as headache, dizziness, vomiting, fever, decreased muscle strength, diplopia or even altered consciousness with seizures in severe patients. Nine patients (90%) showed lateral ventricle dilatation or intracranial infectious lesions on brain CT. Cerebrospinal fluid findings included elevated intracranial pressure, increased leukocyte count, low glucose, low chloride and high cerebrospinal fluid protein. The median CD4 + T count of patients was 104 cells/μL (IQR, 36-224 cells/μL) at the onset of the disease. The CD4 + T cell counts of three patients who eventually died were significantly lower (W = 6.00, p = 0.020) than those of the patients who survived. Conclusions: The common clinical symptoms of T. marneffei central nervous system infection are associated with high intracranial pressure and intracranial infectious lesions. Earlier recognition and diagnosis and a prolonged course of amphotericin B treatment followed by itraconazole combined with early ART might reduce the mortality rate.

BackgroundPsoriasis is a common inflammatory skin disease that has a great impact on patients’ physical and mental health. However, the causes and underlying molecular mechanisms of psoriasis are still largely unknown.MethodsThe expression profiles of genes from psoriatic lesion samples and skin samples from healthy controls were integrated via the sva software package, and differentially expressed genes (DEGs) between psoriasis and healthy skin were screened by the limma package. Furthermore, GO and KEGG pathway enrichments for the DEGs were performed using the Clusterprofiler package. Protein–protein interaction (PPI) networks for the DEGs were then constructed to identify hub genes. scGESA analysis was performed on a single-cell RNA sequencing dataset via irGSEA. In order to find the cytokines correlated with the hub genes expression, single cell weighted gene co-expression network analyses (scWGCNA) were utilized to build a gene co-expression network. Furthermore, the featured genes of psoriasis found in suprabasal keratinocytes were intersected with hub genes. We then analyzed the expression of the intersection genes and cytokines in the integrated dataset. After that, we used other datasets to reveal the changes in the intersection genes’ expression levels during biological therapy. The relationship between intersection genes and PASI scores was also explored.ResultsWe identified 148 DEGs between psoriatic and healthy samples. GO and KEGG pathway enrichment analysis suggested that DEGs are mainly involved in the defense response to other organisms. The PPI network showed that 11 antiviral proteins (AVPs) were hub genes. scGSEA analysis in the single-cell transcriptome dataset showed that those hub genes are highly expressed in keratinocytes, especially in suprabasal keratinocytes. ISG15, MX1, IFI44L, and IFI27 were the characteristic genes of psoriasis in suprabasal keratinocytes. scWGCNA showed that three cytokines—IL36G, MIF, and IL17RA—were co-expressed in the turquoise module. Only interleukin-36 gamma (IL36G) was positively correlated with AVPs in the integrated dataset. IL36G and AVPs were found co-expressed in a substantial number of suprabasal keratinocytes. Furthermore, we found that the expression levels of IL36G and the 4 AVPs showed positive correlation with PASI score in patients with psoriasis, and that these levels decreased significantly during treatment with biological therapies, but not with methotrexate.ConclusionIL36G and antiviral proteins may be closely related with the pathogenesis of psoriasis, and they may represent new candidate molecular markers for the occurrence and severity of psoriasis.