Co-Infection Talaromyces marneffei and Pneumocystis jirovecii in a Patient with Systemic Lupus Erythematosus.

Talaromyces marneffei (TM) and Pneumocystis jirovecii (PJ) infection are opportunistic infections that typically affect individuals with compromised immune systems, such as those with HIV or immunodeficiency. However, these infections are rarely seen in patients with systemic lupus erythematosus (SLE). We present a case study of a 52-year-old woman diagnosed with SLE who developed a co-infection of TM and PJ after receiving glucocorticoids, mycophenolate mofetil (MMF), and belimumab therapy. The patient's pneumonia improved following treatment with voriconazole, clarithromycin, and compound sulfamethoxazole. This case highlights the potential risk of serious opportunistic infections in SLE patients receiving a combination of glucocorticoids, MMF, and belimumab. Close monitoring of lymphocyte count, immunoglobulin levels, and chest computed tomography scans can aid in the early detection of infections. To the best of our knowledge, this is the first reported case of TM and PJ co-infection in an SLE patient.

Talaromyces marneffei Can Capture CD86 Proteins of Macrophages in vitro.

Background: Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus endemic to Southeast Asia that causes human systemic infection. Our earlier immunohistochemical studies revealed that the organisms were markedly labeled with the CD86 antigen in cutaneous lesions brought on by infection. However, the relationship between T. marneffei and the CD86 co-stimulatory molecule is still unknown. Objective: To explore the association between CD86 Protein and Talaromyces marneffei organisms in vitro and discuss the potential mechanisms. Methods: We created the CD86-EGFP fusion protein in THP-1 macrophages and co-cultured T. marneffei conidia with it. We used confocal fluorescence microscopy to view in vitro dynamics. The link between CD86 Protein and Talaromyces marneffei organisms in vitro was discovered using immunoelectron microscopy, indirect immunofluorescence test, and immunohistochemistry assay. Results: T. marneffei cells received soluble CD86-EGFP from THP-1 macrophages detected by confocal fluorescent microscopy. Both the indirect immunofluorescence assay and the immunohistochemical assay showed that T. marneffei conidia were stained by the CD86 marker. Immunoelectron microscopy showed that characteristic colloidal gold particles were observed in T. marneffei organisms when co-cultured with THP-1 macrophages. Conclusion: T. marneffei organisms have the ability to capture CD86 proteins from macrophages in vitro.

Overexpression of CD86 enhances the ability of THP-1 macrophages to defend against Talaromyces marneffei.

BACKGROUND: Macrophages are the first line of defense against Talaromyces marneffei. CD86 is a surface molecule expressed on antigen-presenting cells, such as macrophages, that provide costimulatory signals necessary for T cell activation and survival. In a prior study, it was shown that as infection progressed, CD86 expression levels in macrophages considerably declined while CD86 concentrations in the supernatant significantly increased. Additionally, M1 macrophage polarization was insufficient and switched to M2 macrophage polarization. Besides costimulation, however, additional roles of CD86 are not known or well-studies. Therefore, we hypothesized that upregulating CD86 on macrophages might promote T. marneffei defense. METHODS: A lentivirus vector, called Lenti-CD86, was used to infect THP-1 cells to overexpress secretory CD86. Through killing assay, nitric oxide detection, and cytokine detection, the capacity of THP-1 macrophages to phagocytose and kill T. marneffei was examined. RESULTS: In the current study, Lenti-CD86 transfection of THP-1 cells resulted in a signifant expression of CD86. Additionally, the THP-1 macrophages stably transfected with Lenti-CD86 showed higher nitric oxide and IL-1ß production, faster polarization, and stronger phagocytosis and killing capabilities than the non-transfected or control virus transfected cells. CONCLUSION: Our study shows that lentivirus-mediated CD86 overexpression improves THP-1 macrophages' capacity to phagocytose and eliminate T. marneffei.

Talaromyces marneffei Influences Macrophage Polarization and Sterilization Ability via the Arginine Metabolism Pathway in Vitro.

The opportunistic fungal pathogen Talaromyces marneffei, which is endemic across a narrow band of tropical Southeast Asia and southern China, is an intracellular pathogen that causes systemic and lethal infection through the mononuclear phagocyte system. The mechanisms by which T. marneffei successfully replicates and escapes the immune system remain unclear. To investigate the role of arginine metabolism in the escape of T. marneffei from killer macrophages, we assessed inducible nitric oxide synthase (iNOS) and arginase expression, nitric oxide (NO) production, arginase and phagocytic activity, and the killing of T. marneffei in a coculture system. Our results indicate that T. marneffei induced macrophage polarization toward the M2 phenotype and regulated the arginine metabolism pathway by prolonging infection, thereby reducing antimicrobial activity and promoting fungal survival. Moreover, inhibiting T. marneffei-induced macrophage arginase activity with Nω-hydroxy-nor-arginine restored NO synthesis and strengthened fungal killing. These findings indicate that T. marneffei affects macrophage polarization and inhibits macrophage antimicrobial function via the arginine metabolism pathway.

The Effect of Talaromyces marneffei Infection on CD86 Expression in THP-1 Cells.

BACKGROUND: Talaromyces marneffei (T. marneffei) is a destructive opportunistic dimorphic fungal which can cause lethiferous Talaromycosis, but the clearance of T. marneffei mainly depends on the innate immune response. OBJECTIVE: To investigate whether T. marneffei can inhibit the expression of CD86 in THP-1 cells after infection and discuss the potential mechanisms. METHODS: Western blot and immunoelectron microscopy were used to detect the CD86 expression on T. marneffei cultured on BHI medium at 37°C. Western blot, enzyme-linked immunoassay and immunofluorescence were used to detect the change of CD86 expression on macrophages incubating with T. marneffei. Enzyme-linked immunoassay was used to detect the content of CD86 in supernatant in the co-culture system. Immunohistochemistry and immunoelectron microscopy were used to detect the expression of CD86 on T. marneffei incubating with macrophages. RESULTS: T. marneffei did not express CD86 when cultured separately at 37°C detected by Western blot and immunoelectron microscopy, but it did express CD86 when incubated with macrophages detected by immunohistochemistry and immunoelectron microscopy. The CD86 expression of macrophages significantly decreased at 72 hours when infected with T. marneffei while the content of CD86 in supernatant significantly increased at 72 hours compared with the control group which were detected by Western blot, enzyme-linked immunoassay and immunofluorescence. CONCLUSION: 1) After T. marneffei infection, CD86 expression on THP-1 decreased, and with the progression of infection, insufficient polarization of M1 macrophages gradually appeared; 2) T. marneffei may adsorb or uptake CD86 in supernatant produced by macrophages during the contact with THP-1 cells, thus leading to the consumption of CD86 in macrophages.

[Efficacy observation on chronic tension-type headache treated with acupuncture at galea tendon-muscle node].

OBJECTIVE: To explore the better therapy for chronic tension-type headache (CTTH). METHODS: Two hundred and eighty-eight cases were randomized into a sticking needling group (150 cases) and an acupuncture group (138 cases). In the sticking needling group, the manual sticking needling technique was adopted to stimulate the galea tendon-muscle node. In the acupuncture group, the conventional acupuncture therapy was applied to Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Taiyang (EX-HN 5), Touwei (ST 18), Hegu (LI 4), etc. The treatment was given once a day, and 30 days made one session. After two sessions of treatment and after three months follow-up, CTTH score (including the score of headache attack frequency and the score of headache severity) was observed and compared before and after treatment separately. The efficacy was evaluated in two groups. RESULTS: CTTH score was all reduced after treatment in the two groups (both P<0.01), the score in the sticking needling group was lower than that in the acupuncture group (2.38 +/- 1.22 vs 4.16 +/- 2.54, P < 0.01). The effective rate was 97.3% (146/150) in the sticking needling group, which was better than 88.4% (122/138) in the acupuncture group (P < 0.05). CONCLUSION: The manual sticking needling technique at galea tendon-muscle node achieves the superior results of reducing the pain attack frequency and severity of CTTH as compared with the acupuncture therapy of the routine acupoint selection.