Medical Microbiology and Immunology最新文献

{"title":"Programmed cell death-1 single-nucleotide polymorphism rs10204525 is associated with human immunodeficiency virus type 1 RNA viral load in HIV-1-infected Moroccan subjects.","authors":"Hanâ Baba,&nbsp;Anass Kettani,&nbsp;Meryem Bouqdayr,&nbsp;Ahd Ouladlahsen,&nbsp;Rajaa Bensghir,&nbsp;Latifa Marih,&nbsp;Mustapha Sodqi,&nbsp;Soumaya Benjelloun,&nbsp;Sayeh Ezzikouri,&nbsp;Imane Zaidane,&nbsp;Fatima-Zahra Jadid,&nbsp;Kamal Marhoum El Filali,&nbsp;Lahcen Wakrim","doi":"10.1007/s00430-021-00712-7","DOIUrl":"https://doi.org/10.1007/s00430-021-00712-7","url":null,"abstract":"<p><p>Human Immunodeficiency Virus (HIV-1) infections are characterized by dysfunctional cellular and humoral antiviral immune responses. The progressive loss of effector functions in chronic viral infection has been associated with the up-regulation of programmed death-1 (PD-1), a negative regulator of activated T cells and Natural Killer cells. In HIV-1 infection, increased levels of PD-1 expression correlate with CD8 + T-cell exhaustion. In vitro, PD-1 blockade using PD-1 antibodies led to an increase in HIV-1 specific CD8 + T and memory B cell proliferation. We aimed to investigate the impact of PDCD1 rs10204525 polymorphism on HIV-1 susceptibility, AIDS development, and treatment response outcomes in HIV-1 infection in a Moroccan population. A total of 214 HIV-1 seropositive and 250 seronegative subjects were enrolled to investigate the association between the between the single-nucleotide polymorphism (SNP) rs10204525 of PDCD1 gene and HIV-1 pathogenesis using a predesigned TaqMan SNP genotyping assay. No significant association was found between rs10204525 and susceptibility to HIV-1 infection and AIDS development (p > 0.05). Genotype frequencies were significantly associated with the viral load before ART (p = 0.0105). HIV-1 viral load was significantly higher among subjects with the CC compared to TT genotype (p = 0.0043). In treated subjects, the median of viral load levels was significantly higher in CC and CT groups than TT subjects (p < 0.005). However, analysis of the correlation between CD4 + T-cell levels and PDCD1 polymorphism before and after ART showed no significant difference (p > 0.05). Our results demonstrated that rs10204525 polymorphism does not affect HIV-1 infection. However, this polymorphism may affect the response to treatment as measured by RNA viral load levels.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00430-021-00712-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39015388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmission of cell-associated human cytomegalovirus isolates between various cell types using polymorphonuclear leukocytes as a vehicle.","authors":"Berenike Braun,&nbsp;Christian Sinzger","doi":"10.1007/s00430-021-00713-6","DOIUrl":"https://doi.org/10.1007/s00430-021-00713-6","url":null,"abstract":"<p><p>Polymorphonuclear leukocytes (PMNs) are regarded as vehicles for the hematogenous dissemination of human cytomegalovirus (HCMV). In cell culture, this concept has been validated with cell-free laboratory strains but not yet with clinical HCMV isolates that grow strictly cell-associated. We, therefore, aimed to evaluate whether PMNs can also transmit such isolates from initially infected fibroblasts to other cell types, which might further clarify the role of PMNs in HCMV dissemination and provide a model to search for potential inhibitors. PMNs, which have been isolated from HCMV-seronegative individuals, were added for 3 h to fibroblasts infected with recent cell-associated HCMV isolates, then removed and transferred to various recipient cell cultures. The transfer efficiency in the recipient cultures was evaluated by immunofluorescence staining of viral immediate early antigens. Soluble derivatives of the cellular HCMV entry receptor PDGFRα were analyzed for their potential to interfere with this transfer. All of five tested HCMV isolates could be transferred to fibroblasts, endothelial and epithelial cells with transfer rates ranging from 2 to 9%, and the transferred viruses could spread focally in these recipient cells within 1 week. The PDGFRα-derived peptides IK40 and GT40 reduced transfer by 40 and 70% when added during the uptake step. However, when added during the transfer step, only IK40 was effective, inhibiting transmission by 20% on endothelial cells and 50-60% on epithelial cells and fibroblasts. These findings further corroborate the assumption of cell-associated HCMV dissemination by PMNs and demonstrate that it is possible to inhibit this transmission mode.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00430-021-00713-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39065980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Head-to-head performance comparison of self-collected nasal versus professional-collected nasopharyngeal swab for a WHO-listed SARS-CoV-2 antigen-detecting rapid diagnostic test.","authors":"Julian A F Klein,&nbsp;Lisa J Krüger,&nbsp;Frank Tobian,&nbsp;Mary Gaeddert,&nbsp;Federica Lainati,&nbsp;Paul Schnitzler,&nbsp;Andreas K Lindner,&nbsp;Olga Nikolai,&nbsp;B Knorr,&nbsp;A Welker,&nbsp;Margaretha de Vos,&nbsp;Jilian A Sacks,&nbsp;Camille Escadafal,&nbsp;Claudia M Denkinger","doi":"10.1007/s00430-021-00710-9","DOIUrl":"10.1007/s00430-021-00710-9","url":null,"abstract":"<p><p>In 2020, the World Health Organization (WHO) recommended two SARS-CoV-2 lateral flow antigen-detecting rapid diagnostics tests (Ag-RDTs), both initially with nasopharyngeal (NP) sample collection. Independent head-to-head studies are necessary for SARS-CoV-2 Ag-RDT nasal sampling to demonstrate comparability of performance with nasopharyngeal (NP) sampling. We conducted a head-to-head comparison study of a supervised, self-collected nasal mid-turbinate (NMT) swab and a professional-collected NP swab, using the Panbio™ Ag-RDT (distributed by Abbott). We calculated positive and negative percent agreement between the sampling methods as well as sensitivity and specificity for both sampling techniques compared to the reference standard reverse transcription polymerase chain reaction (RT-PCR). A SARS-CoV-2 infection could be diagnosed by RT-PCR in 45 of 290 participants (15.5%). Comparing the NMT and NP sampling the positive percent agreement of the Ag-RDT was 88.1% (37/42 PCR positives detected; CI 75.0-94.8%). The negative percent agreement was 98.8% (245/248; CI 96.5-99.6%). The overall sensitivity of Panbio with NMT sampling was 84.4% (38/45; CI 71.2-92.3%) and 88.9% (40/45; CI 76.5-95.5%) with NP sampling. Specificity was 99.2% (243/245; CI 97.1-99.8%) for both, NP and NMT sampling. The sensitivity of the Panbio test in participants with high viral load (> 7 log₁₀ SARS-CoV-2 RNA copies/mL) was 96.3% (CI 81.7-99.8%) for both, NMT and NP sampling. For the Panbio supervised NMT self-sampling yields comparable results to NP sampling. This suggests that nasal self-sampling could be used for to enable scaled-up population testing.Clinical Trial DRKS00021220.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00430-021-00710-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39026355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of cigarette smoke extract on bronchial epithelial cells stimulated with Cryptococcus neoformans.","authors":"Aline Beatriz Mahler Pereira,&nbsp;Jhony Robison Oliveira,&nbsp;Ana Leticia Julio Souza,&nbsp;Leonardo Andrade-Silva,&nbsp;Marcos Vinicius Silva,&nbsp;Paulo Roberto Silva,&nbsp;Mario Leon Silva-Vergara,&nbsp;Alexandre Paula Rogerio","doi":"10.1007/s00430-021-00715-4","DOIUrl":"https://doi.org/10.1007/s00430-021-00715-4","url":null,"abstract":"<p><p>In the airways, the adhesion of Cryptococcus neoformans with airway epithelial cells is crucial for the establishment of cryptococcosis. Tobacco smoke is considered a risk factor for cryptococcosis. Here, we evaluated the effects of cigarette smoke extract (CSE) on human bronchial epithelial cells (BEAS-2B) stimulated with C. neoformans. Multiplicities of infection (MOIs) of 1-100 of C. neoformans per cell led to increased IL-8 production and no cytotoxic effects when compared to those of controls. C. neoformans (MOI 100) also significantly increased the concentration of IL-6. In cells stimulated with CSE doses (1.0, 2.5 and 5.0%) from one or five cigarettes, increased IL-1β production was observed only in doses from one (1.0%) and five (2.5%) cigarettes when compared to that of controls. However, only 1.0% CSE failed to show cytotoxic effects. In addition, CSE significantly increased the concentration of IL-8. Cells stimulated with both CSE and C. neoformans demonstrated a reduction in IL-6/STAT3 signalling compared to that in cells stimulated by C. neoformans. In addition, a significant increase in IL-10 production was also observed. No alterations in NF-kB or ICAM-1 expression were observed among the groups. The combination of CSE and C. neoformans favoured the increase of fungal numbers and extracellular adhering of C. neoformans on BEAS-2B cells. In addition, the internalization of C. neoformans on BEAS-2B cells was reduced after CSE stimulation. In conclusion, the association of CSE and C. neoformans induced an anti-inflammatory effect in bronchial epithelial cells, which might favour the development of C. neoformans infection in the airways.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00430-021-00715-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39074254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of stability and inactivation methods of SARS-CoV-2 in context of laboratory settings.","authors":"Marek Widera, Sandra Westhaus, Holger F Rabenau, Sebastian Hoehl, Denisa Bojkova, Jindrich Cinatl, Sandra Ciesek","doi":"10.1007/s00430-021-00716-3","DOIUrl":"10.1007/s00430-021-00716-3","url":null,"abstract":"<p><p>The novel coronavirus SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. Laboratory work with SARS-CoV-2 in a laboratory setting was rated to biosafety level 3 (BSL-3) biocontainment level. However, certain research applications in particular in molecular biology require incomplete denaturation of the proteins, which might cause safety issues handling contaminated samples. In this study, we evaluated lysis buffers that are commonly used in molecular biological laboratories for their ability to inactivate SARS-CoV-2. In addition, viral stability in cell culture media at 4 °C and on display glass and plastic surfaces used in laboratory environment was analyzed. Furthermore, we evaluated chemical and non-chemical inactivation methods including heat inactivation, UV-C light, addition of ethanol, acetone-methanol, and PFA, which might be used as a subsequent inactivation step in the case of insufficient inactivation. We infected susceptible Caco-2 and Vero cells with pre-treated SARS-CoV-2 and determined the tissue culture infection dose 50 (TCID₅₀) using crystal violet staining and microscopy. In addition, lysates of infected cells and virus containing supernatant were subjected to RT-qPCR analysis. We have found that guanidine thiocyanate and most of the tested detergent containing lysis buffers were effective in inactivation of SARS-CoV-2, however, the M-PER lysis buffer containing a proprietary detergent failed to inactivate the virus. In conclusion, careful evaluation of the used inactivation methods is required especially for non-denaturing buffers. Additional inactivation steps might be necessary before removal of lysed viral samples from BSL-3.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39125904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The human symbiont Mucispirillum schaedleri: causality in health and disease.","authors":"Simone Herp, Abilash Chakravarthy Durai Raj, Marta Salvado Silva, Simon Woelfel, Bärbel Stecher","doi":"10.1007/s00430-021-00702-9","DOIUrl":"10.1007/s00430-021-00702-9","url":null,"abstract":"<p><p>Trillions of bacteria inhabit the mammalian gastrointestinal tract. In the majority of hosts, these symbionts contribute largely to beneficial functions promoting microbe-host homeostasis. However, an increasing number of human diseases is associated with altered microbiota composition and enrichment of certain bacterial species. A well-known example of this is Mucispirillum schaedleri, which has been associated with inflammatory conditions in the intestine. Mucispirillum spp. belong to the phylum Deferribacteres and are prevalent but low abundant members of the rodent, pig and human microbiota. Recently, M. schaedleri was causally linked to the development of Crohn's disease-like colitis in immunodeficient mice. While this study certifies a considerable pathogenic potential, the same organism can also promote health in the immunocompetent host: M. schaedleri protects from Salmonella enterica serovar Typhimurium (S. Tm)-induced colitis by interfering with the expression of the pathogen´s invasion machinery. In this review, we summarize the current knowledge on the mammalian gut symbiont M. schaedleri and its role in intestinal homeostasis and discuss open questions and perspectives for future research.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38937253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contributing role of TNF, IL-10, sTNFR1 and TNF gene polymorphisms in disease severity of leptospirosis.","authors":"Thilini Nisansala, Manjula Weerasekera, Nilantha Ranasinghe, Chamil Marasinghe, Chandika Gamage, Neluka Fernando, Chinthika Gunasekara","doi":"10.1007/s00430-021-00714-5","DOIUrl":"10.1007/s00430-021-00714-5","url":null,"abstract":"<p><p>The immune response is hypothesized as an important factor in the disease outcome of leptospirosis. Exaggerated immune response may promote tissue damage that lead to severe disease outcome. In this study TNF, IL-10, sTNFR1 levels were measured among sixty-two hospitalized leptospirosis confirmed patients in Sri Lanka. Thirty-one serum samples from healthy individuals were obtained as controls. PCR-RFLP method was used to identify TNF gene polymorphisms and to determine their association with TNF expression and disease severity in leptospirosis. TNF (p = 0.0022) and IL-10 (p < 0.0001) were found to be significantly elevated in leptospirosis patients, while sTNFR1 (p < 0.0001) was significantly suppressed. TNF was not significantly elevated in patients with complications while the anti-inflammatory cytokine IL-10 was significantly elevated among patients with complications (p = 0.0011) and with mortality (p = 0.0088). The ratio of IL-10 to TNF was higher among patients with complications (p = 0.0008) and in fatal cases (p = 0.0179). No association between TNF gene polymorphisms and TNF expression was detected due to the low frequency of heterozygous and mutated genes present in this study population. Thus the findings of the study show that elevated levels of IL-10 in the acute phase of disease could lead to severe outcomes and a high IL-10/TNF ratio is observed in patients with complications due to leptospirosis.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39121788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of specific in-vitro virulence gene expression and innate host response in locally invasive vs colonizer strains of Streptococcus pneumoniae.","authors":"Naoko Fuji,&nbsp;Michael E Pichichero,&nbsp;Ravinder Kaur","doi":"10.1007/s00430-021-00701-w","DOIUrl":"https://doi.org/10.1007/s00430-021-00701-w","url":null,"abstract":"<p><p>Among Rochester NY children, a dramatic increase in nasopharyngeal (NP) colonization by non-vaccine pneumococcal serotypes 35B and 15A occurred during years 2010-2015, after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). In our population, serotype 35B strains colonized in the nasopharynx (NP) but infrequently caused acute otitis media (AOM) whereas serotype 15A strains displayed virulence, evidenced by causing AOM. To explain the virulence difference, virulence genes expression between 35B and 15A, as well as the host's immune response during asymptomatic colonization were analyzed. We investigated differences in regulation of 19 virulence genes for differences in virulence using RT-PCR in 20 35B and 14 15A strains and measured gene expression of 9 host innate cytokines in the NP to assess the mucosal inflammatory response during asymptomatic colonization. Comparing 35B versus 15A strains, genes for competence ComA and RrgC were upregulated; capsular (Cps2D) and virulence genes (PfbA, PcpA and PhtE) were downregulated among 35B strains. PavB, LytA, LytB, NanA, CiaR, PhtD, LuxS, PspA and pneumolysin (Ply) showed no difference. IL17 and IL23 gene expression were > tenfold higher during 35B compared to 15A strain asymptomatic colonization. Only IL23 showed significant difference. In the first 5 years after introduction of PCV13, serotype 35B strains emerged as asymptomatic colonizers and 15A strains emerged to cause AOM in young children. Various genes (PfbA, PcpA, Cps2D and PhtE) among tested in this analysis were downregulated in 35B whereas ComA and RrgC were significantly upregulated. For the host's cytokine response, IL23 proinflammatory response which is essential for the differentiation of Th17 lymphocytes in the NP of children with 35B strains was significantly higher than the response to 15A during asymptomatic colonization.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00430-021-00701-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25504446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of HIF-1α in BCG-stimulated macrophages polarization and their tumoricidal effects in vitro.","authors":"Pei Zhu,&nbsp;Yuyang Hou,&nbsp;Mengyan Tang,&nbsp;Zheng Jin,&nbsp;Youran Yu,&nbsp;Dong Li,&nbsp;Dongmei Yan,&nbsp;Zehua Dong","doi":"10.1007/s00430-021-00708-3","DOIUrl":"https://doi.org/10.1007/s00430-021-00708-3","url":null,"abstract":"<p><p>BCG is widely used for cancer treatment, where macrophages play an important role. However, the mechanism of BCG affecting macrophages remains poorly understood. In this study, we used BCG to stimulate myeloid-derived macrophages lacking HIF-1α, the levels of TNF-α, IL-1β, CD86 of macrophages and their effects on the growth of tumor cells MCA207 and B16-F10 were detected. We found that the absence of HIF-1α prevents BCG-stimulated macrophages from polarizing towards the M (BCG) and attenuating its killing effect on tumor cells. In addition, we demonstrated that the tumors of mice lacking HIF-1α in macrophages were significantly increased by the experiment of mice transplantation. Our study provides relevant evidence for exploring the mechanism of the BCG vaccine in the prevention and treatment of related diseases.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00430-021-00708-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38970130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acarbose presents in vitro and in vivo antileishmanial activity against Leishmania infantum and is a promising therapeutic candidate against visceral leishmaniasis.","authors":"Rafaella R Costa,&nbsp;João A Oliveira-da-Silva,&nbsp;Thiago A R Reis,&nbsp;Grasiele S V Tavares,&nbsp;Débora V C Mendonça,&nbsp;Camila S Freitas,&nbsp;Daniela P Lage,&nbsp;Vívian T Martins,&nbsp;Luciana M R Antinarelli,&nbsp;Amanda S Machado,&nbsp;Raquel S Bandeira,&nbsp;Fernanda Ludolf,&nbsp;Thaís T O Santos,&nbsp;Rory C F Brito,&nbsp;Maria V Humbert,&nbsp;Daniel Menezes-Souza,&nbsp;Mariana C Duarte,&nbsp;Miguel A Chávez-Fumagalli,&nbsp;Bruno M Roatt,&nbsp;Elaine S Coimbra,&nbsp;Eduardo A F Coelho","doi":"10.1007/s00430-021-00707-4","DOIUrl":"https://doi.org/10.1007/s00430-021-00707-4","url":null,"abstract":"<p><p>Treatment against visceral leishmaniasis (VL) is mainly hampered by drug toxicity, long treatment regimens and/or high costs. Thus, the identification of novel and low-cost antileishmanial agents is urgent. Acarbose (ACA) is a specific inhibitor of glucosidase-like proteins, which has been used for treating diabetes. In the present study, we show that this molecule also presents in vitro and in vivo specific antileishmanial activity against Leishmania infantum. Results showed an in vitro direct action against L. infantum promastigotes and amastigotes, and low toxicity to mammalian cells. In addition, in vivo experiments performed using free ACA or incorporated in a Pluronic^® F127-based polymeric micelle system called ACA/Mic proved effective for the treatment of L. infantum-infected BALB/c mice. Treated animals presented significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes when compared to the controls, as well as the development of antileishmanial Th1-type humoral and cellular responses based on high levels of IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and IgG2a isotype antibodies. In addition, ACA or ACA-treated animals suffered from low organ toxicity. Treatment with ACA/Mic outperformed treatments using either Miltefosine or free ACA based on parasitological and immunological evaluations performed one and 15 days post-therapy. In conclusion, data suggest that the ACA/Mic is a potential therapeutic agent against L. infantum and merits further consideration for VL treatment.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00430-021-00707-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38820110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}