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PURPOSE OF REVIEW: Emerging technologies are revolutionizing parasitology diagnostics and challenging traditional methods reliant on microscopic analysis or serological confirmation, which are known for their limitations in sensitivity and specificity. This article sheds light on the transformative potential of artificial intelligence and molecular assays in the field, promising more accurate and efficient detection methods. RECENT FINDINGS: Artificial intelligence has emerged as a promising tool for blood and stool parasite review, when paired with comprehensive databases and expert oversight result in heightened specificity and sensitivity of diagnoses while also increasing efficiency. Significant strides have been made in nucleic acid testing for multiplex panels for enteric pathogen. Both multiplex and single target panels for Plasmodium, Babesia, filaria, and kinetoplastids have been developed and garnered regulatory approval, notably for blood donor screening in the United States. Additional technologies such as MALDI-TOF, metagenomics, flow cytometry, and CRISPR-Cas are under investigation for their diagnostic utility and are currently in the preliminary stages of research and feasibility assessment. SUMMARY: Recent implementation of artificial intelligence and digital microscopy has enabled swift smear screening and diagnosis, although widespread implementation remains limited. Simultaneously, molecular assays - both targeted and multiplex panels are promising and have demonstrated promise in numerous studies with some assays securing regulatory approval recently. Additional technologies are under investigation for their diagnostic utility and are compelling avenues for future proof-of-concept diagnostics.
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The growing transition to digital microbiology in clinical laboratories creates the opportunity to interpret images using software. Software analysis tools can be designed to use human-curated knowledge and expert rules, but more novel artificial intelligence (AI) approaches such as machine learning (ML) are being integrated into clinical microbiology practice. These image analysis AI (IAAI) tools are beginning to penetrate routine clinical microbiology practice, and their scope and impact on routine clinical microbiology practice will continue to grow. This review separates the IAAI applications into 2 broad classification categories: (i) rare event detection/classification or (ii) score-based/categorical classification. Rare event detection can be used for screening purposes or for final identification of a microbe including microscopic detection of mycobacteria in a primary specimen, detection of bacterial colonies growing on nutrient agar, or detection of parasites in a stool preparation or blood smear. Score-based image analysis can be applied to a scoring system that classifies images in toto as its output interpretation and examples include application of the Nugent score for diagnosing bacterial vaginosis and interpretation of urine cultures. The benefits, challenges, development, and implementation strategies of IAAI tools are explored. In conclusion, IAAI is beginning to impact the routine practice of clinical microbiology, and its use can enhance the efficiency and quality of clinical microbiology practice. Although the future of IAAI is promising, currently IAAI only augments human effort and is not a replacement for human expertise.
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Inteligência Artificial , Aprendizado de Máquina , Feminino , Humanos , Software , Processamento de Imagem Assistida por Computador , UrináliseRESUMO
The BCL-2 prosurvival protein is implicated in HIV persistence and is a potential therapeutic target for HIV eradication efforts. We now know that cells harboring HIV are preferentially enriched for high BCL-2 expression, enabling their survival, and that the BCL-2 inhibitor venetoclax promotes the death of actively replicating HIV-infected cells in vitro and ex vivo. Herein, we assess the effect of venetoclax on immune clearance of infected cells and show that BCL-2 inhibition significantly enhances target cell killing induced by Fas ligand, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and perforin/granzyme B and synergistically enhances autologous NK (natural killer) and CD8 cells' killing of target cells. In a humanized mouse model of acute HIV infection, venetoclax monotherapy significantly decreases plasma viremia and normalizes CD4:CD8 ratios, and results in more mice with undetectable provirus levels than control. In this model, treatment was associated with leukopenia, as has been described clinically in patients receiving venetoclax for other indications. These data confirm meaningful anti-HIV effects of venetoclax during HIV infection but suggest that venetoclax use should be combined with ART (antiretroviral therapy) to reduce toxicity. IMPORTANCE This study is the first to examine the applicability of BCL-2 inhibition in the setting of active HIV infection in vivo. Furthermore, this study demonstrates that venetoclax significantly enhances target cell killing induced by Fas ligand, TRAIL, and perforin/granzyme B and synergistically enhances autologous NK and CD8 cells' killing of target cells.
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Infecções por HIV , Proteínas Proto-Oncogênicas c-bcl-2 , Animais , Camundongos , Proteína Ligante Fas/metabolismo , Granzimas/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Perforina/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Antirretrovirais/uso terapêuticoRESUMO
Preexisting immunity to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was nonexistent in humans, which coupled with high transmission rates of certain SARS-CoV-2 variants and limited vaccine uptake or availability, has collectively resulted in an ongoing global pandemic. The identification and establishment of one or multiple correlates of protection (CoP) against infectious pathogens is challenging, but beneficial from both the patient care and public health perspectives. Multiple studies have shown that neutralizing antibodies, whether generated following SARS-CoV-2 infection, vaccination, or a combination of both (i.e., hybrid immunity), as well as adaptive cellular immune responses, serve as CoPs for COVID-19. However, the diverse number and type of serologic assays, alongside the lack of cross-assay standardization and emergence of new SARS-CoV-2 variants with immune evasive characteristics, have collectively posed challenges to determining a robust CoP 'threshold' and for the routine utilization of these assays to document 'immunity,' as is commonly done for other vaccine preventable diseases. Here, we discuss what CoPs are, review our current understanding of infection-induced, vaccine-elicited and hybrid immunity to COVID-19 and summarize the current and potential future utility of SARS-CoV-2 serologic testing.
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COVID-19 , Resistência à Doença , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Resistência à Doença/imunologia , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , VacinaçãoRESUMO
The detection of antibodies against Histoplasma capsulatum remains a frequently relied-on approach to diagnose histoplasmosis. We retrospectively assessed the performances of complement fixation (CF) and immunodiffusion (ID) assays for anti-Histoplasma antibody detection in patients with culture-confirmed histoplasmosis at Mayo Clinic (Rochester, MN) over a 10-year period (2011 to 2020). Among 67 culture-confirmed patients who also had H. capsulatum CF/ID testing ordered, 51 (67.1%) were immunocompromised, 34 (50.7%) had localized disease, and 51 (76.1%) presented with <3 months of symptoms before testing. H. capsulatum CF and/or ID testing was positive in 47 (70.1%) patients, with both assays being positive in 39 cases. CF was positive in 44 (65.7%) patients, with reactivity against both H. capsulatum mycelial and yeast antigens in 30 (68.2%) cases, whereas 11 (25%) and 3 (6.8%) individuals had antibodies to the CF yeast or mycelial antigen only, respectively. H. capsulatum ID was positive in 42 (62.7%) patients, with the presence of the M-band only or the H- and M-bands in 27 (64.3%) and 15 (35.7%) cases, respectively. Among 18 serially tested patients, 12 remained ID and/or CF positive at the final time point (median, 154 days; range, 20 to 480 days). Serial CF testing showed that antibodies to the mycelial antigen serorevert to negative more frequently (6/11) than antibodies to the yeast antigen (2/13). There was no statistically significant difference in antibody positivity relative to patient immune status, degree of disease dissemination, or symptom duration. Serologic testing remains a valuable asset to support the diagnosis of histoplasmosis, particularly when direct detection methods fail to identify an infection.
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Histoplasmose , Onygenales , Humanos , Histoplasma , Histoplasmose/diagnóstico , Estudos Retrospectivos , Saccharomyces cerevisiae , Anticorpos Antifúngicos , Imunodifusão , Antígenos de FungosRESUMO
Elizabethkingia species are Gram-negative bacilli that were most recently linked to a cluster of infections in the Midwestern United States from 2016 to 2017. Inappropriate empirical and directed antibiotic selection for this organism is common among providers and is an independent risk factor for mortality. Trends in antimicrobial susceptibility profiles of Elizabethkingia species from a referral laboratory over a 10-year period were reviewed. Identification methods used over time varied and included biochemical panels, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and 16S rRNA gene sequencing. Agar dilution was used to conduct antimicrobial susceptibility testing. One hundred seventy-four clinical isolates were included. The lower respiratory tract (20/37; 54%) was the most common specimen source in pediatric patients, whereas blood isolates (62/137; 45%) constituted the most prevalent source in adults. Among the identified species, Elizabethkingia meningoseptica (72/121; 59%) constituted the majority. All Elizabethkingia species tested against minocycline were susceptible (18/18; 100%), and 90% of isolates tested against trimethoprim-sulfamethoxazole (TMP-SMX) (117/130) were susceptible. Of the 12 Elizabethkingia miricola isolates, most of the tested isolates were susceptible to piperacillin-tazobactam (11/12; 92%) and levofloxacin (11/12; 92%), whereas the Elizabethkingia anophelis isolates most often tested susceptible to piperacillin-tazobactam (13/14; 93%). In this study, Elizabethkingia species showed high rates of in vitro susceptibility to minocycline and TMP-SMX. Further studies are needed to investigate the clinical implications of species-level differences in antimicrobial susceptibilities in this genus.
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Infecções por Flavobacteriaceae , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Infecções por Flavobacteriaceae/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Minociclina , Piperacilina , RNA Ribossômico 16S/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tazobactam , Combinação Trimetoprima e SulfametoxazolRESUMO
The antiapoptotic protein BCL2 inhibits death of HIV-infected cells. Previously, we showed that the BCL2 inhibitor venetoclax selectively kills acutely HIV-infected cells and reduces HIV DNA in latently infected CD4 T cells ex vivo after reactivation with anti-CD3/anti-CD28. However, there is a need to identify a combination therapy with venetoclax and a clinically relevant latency reversal agent. Ixazomib is an oral proteasome inhibitor which we have shown reactivates latent HIV and predisposes reactivated cells to cell death. Here, we determined that the combination of venetoclax and ixazomib kills more latently HIV-infected cells and leads to greater reduction in HIV replication than either treatment alone in vitro in a T cell model. However, combination treatment of ex vivo CD4 T cells from antiretroviral therapy (ART)-suppressed, HIV-positive participants resulted in unanticipated and unacceptable nonspecific toxicity in primary cells. Therefore, while we show proof of concept that multiple agents can enhance selective killing of HIV-infected cells, the combination of venetoclax and ixazomib has unacceptable toxicity in primary cells, and so further investigation is needed to identify a clinically relevant latency reversal agent to combine with venetoclax as a novel strategy to reduce the size of the HIV reservoir.IMPORTANCE A cure for HIV would require eliminating cells that contain the virus in a latent form from the body. Current antiretroviral medications are unable to rid the body of latently infected cells. Here, we show that a combination of investigational agents-ixazomib plus venetoclax-which reactivate latent virus and predispose infected cells to apoptosis may reduce latent virus in a T cell model, but at the expense of nonspecific toxicity in primary cells.
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Fármacos Anti-HIV/farmacologia , Compostos de Boro/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Glicina/análogos & derivados , HIV-1/efeitos dos fármacos , Sulfonamidas/farmacologia , Fármacos Anti-HIV/toxicidade , Apoptose/efeitos dos fármacos , Compostos de Boro/toxicidade , Compostos Bicíclicos Heterocíclicos com Pontes/toxicidade , Linfócitos T CD4-Positivos/virologia , Linhagem Celular , Linhagem Celular Tumoral , Células Cultivadas , Quimioterapia Combinada , Glicina/farmacologia , Glicina/toxicidade , HIV-1/fisiologia , Humanos , Células Jurkat , Provírus/efeitos dos fármacos , Sulfonamidas/toxicidade , Resposta a Proteínas não Dobradas , Ativação Viral , Latência Viral , Replicação Viral/efeitos dos fármacosRESUMO
Eradication of HIV-1 by the "kick and kill" strategy requires reactivation of latent virus to cause death of infected cells by either HIV-induced or immune-mediated apoptosis. To date this strategy has been unsuccessful, possibly due to insufficient cell death in reactivated cells to effectively reduce HIV-1 reservoir size. As a possible cause for this cell death resistance, we examined whether leading latency reversal agents (LRAs) affected apoptosis sensitivity of CD4 T cells. Multiple LRAs of different classes inhibited apoptosis in CD4 T cells. Protein kinase C (PKC) agonists bryostatin-1 and prostratin induced phosphorylation and enhanced neutralizing capability of the anti-apoptotic protein BCL2 in a PKC-dependent manner, leading to resistance to apoptosis induced by both intrinsic and extrinsic death stimuli. Furthermore, HIV-1 producing CD4 T cells expressed more BCL2 than uninfected cells, both in vivo and after ex vivo reactivation. Therefore, activation of BCL2 likely contributes to HIV-1 persistence after latency reversal with PKC agonists. The effects of LRAs on apoptosis sensitivity should be considered in designing HIV cure strategies predicated upon the "kick and kill" paradigm.
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Apoptose/efeitos dos fármacos , Infecções por HIV/virologia , HIV-1/patogenicidade , Proteína Quinase C/química , Latência Viral/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/tratamento farmacológico , Humanos , Fosforilação , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ativação Viral/efeitos dos fármacos , Proteína de Morte Celular Associada a bcl/metabolismoAssuntos
Reação em Cadeia da Polimerase , Humanos , Reações Falso-Negativas , Pneumocystis/genética , Pneumocystis/isolamento & purificação , Pneumocystis/classificação , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Reação em Cadeia da Polimerase/métodosRESUMO
In previous studies, we demonstrated that single-chain variable fragments (scFvs) from anti-human immunodeficiency virus (HIV) Env monoclonal antibodies act as entry inhibitors when tethered to the surface of target cells by a glycosyl-phosphatidylinositol (GPI) anchor. Interestingly, even if a virus escapes inhibition at entry, its replication is ultimately controlled. We hypothesized that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also interact with Env in an infected cell, thereby interfering with the infectivity of newly produced virions. Here, we show that expression of the anti-HIV Env GPI-scFvs in virus-producing cells reduced the release of HIV from cells 5- to 22-fold, and infectivity of the virions that were released was inhibited by 74% to 99%. Additionally, anti-HIV Env GPI-scFv X5 inhibited virion production and infectivity after latency reactivation and blocked transmitter/founder virus production and infectivity in primary CD4+ T cells. In contrast, simian immunodeficiency virus (SIV) production and infectivity were not affected by the anti-HIV Env GPI-scFvs. Loss of infectivity of HIV was associated with a reduction in the amount of virion-associated Env gp120. Interestingly, an analysis of Env expression in cell lysates demonstrated that the anti-Env GPI-scFvs interfered with processing of Env gp160 precursors in cells. These data indicate that GPI-scFvs can inhibit Env processing and function, thereby restricting production and infectivity of newly synthesized HIV. Anti-Env GPI-scFvs therefore appear to be unique anti-HIV molecules as they derive their potent inhibitory activity by interfering with both early (receptor binding/entry) and late (Env processing and incorporation into virions) stages of the HIV life cycle.IMPORTANCE The restoration of immune function and persistence of CD4+ T cells in HIV-1-infected individuals without antiretroviral therapy requires a way to increase resistance of CD4+ T cells to infection by both R5- and X4-tropic HIV-1. Previously, we reported that anchoring anti-HIV-1 single-chain variable fragments (scFvs) via glycosyl-phosphatidylinositol (GPI) to the surface of permissive cells conferred a high level of resistance to HIV-1 variants at the level of entry. Here, we report that anti-HIV GPI-scFvs also derive their potent antiviral activity in part by blocking HIV production and Env processing, which consequently inhibits viral infectivity even in primary infection models. Thus, we conclude that GPI-anchored anti-HIV scFvs derive their potent blocking activity of HIV replication by interfering with successive stages of the viral life cycle. They may be effectively used in genetic intervention of HIV-1 infection.
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Linfócitos T CD4-Positivos/metabolismo , Proteínas Ligadas por GPI/metabolismo , Anticorpos Anti-HIV/metabolismo , HIV-1/fisiologia , Processamento de Proteína Pós-Traducional , Anticorpos de Cadeia Única/metabolismo , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Linhagem Celular , Proteínas Ligadas por GPI/genética , Anticorpos Anti-HIV/genética , Humanos , Anticorpos de Cadeia Única/genética , Internalização do Vírus , Replicação Viral , Produtos do Gene env do Vírus da Imunodeficiência Humana/genéticaRESUMO
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets. The detection of hMPV-specific T cells in HSCT recipients who endogenously controlled active infections support the clinical importance of T-cell immunity in mediating protective antiviral effects. Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections.
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Imunoterapia Adotiva , Metapneumovirus/imunologia , Infecções por Paramyxoviridae/terapia , Adulto , Estudos de Viabilidade , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Granzimas/imunologia , Humanos , Imunidade Celular , Hospedeiro Imunocomprometido/imunologia , Epitopos Imunodominantes/imunologia , Interferon gama/imunologia , Leucócitos Mononucleares/virologia , Masculino , Metapneumovirus/isolamento & purificação , Pessoa de Meia-Idade , Infecções por Paramyxoviridae/imunologia , Linfócitos T/virologia , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemAssuntos
Infecções Oportunistas Relacionadas com a AIDS , Síndrome da Imunodeficiência Adquirida , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Síndrome da Imunodeficiência Adquirida/complicações , Diarreia/microbiologia , Fungos , HumanosRESUMO
Tetherin has been characterized as a key factor that restricts viral particles such as HIV and hepatitis C virus on plasma membranes, acts as a ligand of the immunoglobulin-like transcript 7 (ILT7) receptor in tumor cells, and suppresses antiviral innate immune responses mediated by human plasmacytoid dendritic cells. However, the normal cellular function of Tetherin without viral infection is unknown. Here we show that Tetherin not only serves as a substrate of autophagy but itself regulates the initiation of autophagy. Tetherin interacts with the autophagy/mitophagy suppressor LRPPRC and prevents LRPPRC from forming a ternary complex with Beclin 1 and Bcl-2 so that Beclin 1 is released to bind with PI3KCIII (class III PI3K) to activate the initiation of autophagy. Suppression of Tetherin leads to impairment of autophagy, whereas overexpression of Tetherin causes activation of autophagy. Under mitophagic stress, Tetherin is concentrated on mitochondria engulfed in autophagosomes. Tetherin plays a general role in the degradation of autophagosomes containing not only the symbiotic mitochondria but also, possibly, the infected virus. Therefore, Tetherin may enhance autophagy and mitophagy to suppress tumorigenesis, enhance innate immune responses, or prevent T cell apoptosis or pyroptosis.
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Antígenos CD/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteínas de Membrana/metabolismo , Mitofagia , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Beclina-1 , Proteínas Ligadas por GPI/metabolismo , Células HeLa , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Mapas de Interação de ProteínasRESUMO
As infectious disease diagnostics increasingly incorporates molecular techniques, there are unique preanalytical concerns that must be considered. First, noninvasive specimen types that may be inadequate for culture-based diagnostics may be acceptable when using molecular tests. Second, specimen containers must be evaluated for the presence of substances that may interfere with amplification or sequencing reactions. Finally, the capacity of transport, storage, and processing conditions to maintain nucleic acid integrity and avoid contamination must be assessed. This review explores these issues and the effects they may have on result quality.
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Técnicas Microbiológicas , Manejo de Espécimes , Manejo de Espécimes/métodosRESUMO
OBJECTIVES: Recent work has demonstrated that automated fluorescence flow cytometry (FLC) is a potential alternative for the detection and quantification of Plasmodium parasites. The objective of this study was to apply this novel FLC method to detect and quantify Babesia parasites in venous blood and compare results to light microscopy and polymerase chain reaction methods. METHODS: An automated hematology/malaria analyzer (XN-31; Sysmex) was used to detect and quantify B microti-infected red blood cells from residual venous blood samples (n = 250: Babesia positive, n = 170; Babesia negative, n = 80). As no instrument software currently exists for Babesia, qualitative and quantitative machine learning (ML) algorithms were developed to facilitate analysis. RESULTS: Performance of the ML models was verified against the XN-31 software using P falciparum-infected samples. When applied to Babesia-infected samples, the qualitative ML model demonstrated an area under the curve (AUC) of 0.956 (sensitivity, 95.9%; specificity, 83.3%) relative to polymerase chain reaction. For valid scattergrams, the qualitive model achieved an AUC of 1.0 (sensitivity and specificity, 100%), while the quantitative model demonstrated an AUC of 0.986 (sensitivity, 94.4%; specificity, 100%). CONCLUSIONS: This investigation demonstrates that Babesia parasites can be detected and quantified directly from venous blood using FLC. Although promising, opportunities remain to improve the general applicability of the method.
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Babesia , Babesiose , Eritrócitos , Citometria de Fluxo , Citometria de Fluxo/métodos , Humanos , Babesiose/diagnóstico , Babesiose/sangue , Eritrócitos/parasitologia , Babesia/isolamento & purificação , Babesia/genética , Aprendizado de Máquina , Reação em Cadeia da Polimerase/métodos , Sensibilidade e EspecificidadeRESUMO
HIV-1 infection of target cells can occur through either cell-free virions or cell-cell transmission in a virological synapse, with the latter mechanism of infection reported to be 100- to 1,000-fold more efficient. Neutralizing antibodies and entry inhibitors effectively block cell-free HIV-1, but with few exceptions, they display much less inhibitory activity against cell-mediated HIV-1 transmission. Previously, we showed that engineering HIV-1 target cells by genetically linking single-chain variable fragments (scFvs) of antibodies to glycosyl phosphatidylinositol (GPI) potently blocks infection by cell-free virions and cell-mediated infection by immature dendritic cell (iDC)-captured HIV-1. Expression of scFvs on CD4+ cell lines by transduction with X5 derived anti-HIV-1 Env antibody linked to a GPI attachment signal directs GPI-anchored scFvs into lipid rafts of the plasma membrane. In this study, we further characterize the effect of GPI-scFv X5 on cell-cell HIV-1 transmission from DCs to target cells. We report that expression of GPI-scFv X5 in transduced CD4+ cell lines and human primary CD4+ T cells potently restricts viral replication in iDC- or mDC-captured HIV-1 in trans. Using live-cell imaging, we observed that when GPI-GFP or GPI-scFv X5 transduced T cells are co-cultured with iDCs, GPI-anchored proteins enrich in contact zones and subsequently migrate from T cells into DCs, suggesting that transferred GPI-scFv X5 interferes with HIV-1 infection of iDCs. We conclude that GPI-scFv X5 on the surface of transduced CD4+ T cells not only potently blocks cell-mediated infection by DCs, but it transfers from transduced cells to the surface of iDCs and neutralizes HIV-1 replication in iDCs. Our findings have important implications for HIV-1 antibody-based immunotherapies as they demonstrate a viral inhibitory effect that extends beyond the transduced CD4+ T cells to iDCs which can enhance HIV-1 replication.
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Infecções por HIV , Soropositividade para HIV , HIV-1 , Anticorpos de Cadeia Única , Humanos , Linfócitos T CD4-Positivos , Anticorpos Anti-HIV , Linhagem Celular , Anticorpos de Cadeia Única/farmacologiaRESUMO
GATA2 mutation can result in profoundly reduced monocytes, dendritic cells, natural killer cells, and B cells, and is associated with a predisposition for recurrent and disseminated nontuberculous mycobacterial (NTM) infections and myelodysplasias. Herein, we describe a unique case of 3 simultaneous disseminated NTM infections in a patient with GATA2 mutations.