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1.
J Exp Med ; 218(10)2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347010

RESUMO

Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. An influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, using complementary genetic models of eosinophil deficiency, we demonstrate that in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice.

2.
J Immunol ; 207(5): 1239-1249, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389623

RESUMO

HIV-1 infection substantially increases the risk of developing tuberculosis (TB). Mechanisms such as defects in the Th1 response to Mycobacterium tuberculosis in HIV-infected persons have been widely reported. However, Th1-independent mechanisms also contribute to protection against TB. To identify a broader spectrum of defects in TB immunity during HIV infection, we examined IL-17A and IL-22 production in response to mycobacterial Ags in peripheral blood of persons with latent TB infection and HIV coinfection. Upon stimulating with mycobacterial Ags, we observed a distinct CD4+ Th lineage producing IL-22 in the absence of IL-17A and IFN-γ. Mycobacteria-specific Th22 cells were present at high frequencies in blood and contributed up to 50% to the CD4+ T cell response to mycobacteria, comparable in magnitude to the IFN-γ Th1 response (median 0.91% and 0.55%, respectively). Phenotypic characterization of Th22 cells revealed that their memory differentiation was similar to M. tuberculosis-specific Th1 cells (i.e., predominantly early differentiated CD45RO+CD27+ phenotype). Moreover, CCR6 and CXCR3 expression profiles of Th22 cells were similar to Th17 cells, whereas their CCR4 and CCR10 expression patterns displayed an intermediate phenotype between Th1 and Th17 cells. Strikingly, mycobacterial IL-22 responses were 3-fold lower in HIV-infected persons compared with uninfected persons, and the magnitude of responses correlated inversely with HIV viral load. These data provide important insights into mycobacteria-specific Th subsets in humans and suggest a potential role for IL-22 in protection against TB during HIV infection. Further studies are needed to fully elucidate the role of IL-22 in protective TB immunity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Interleucinas/metabolismo , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/fisiologia , Subpopulações de Linfócitos T/imunologia , Adulto , Células Cultivadas , Coinfecção , Feminino , Soropositividade para HIV , Humanos , Interleucina-17/metabolismo , Masculino , África do Sul , Carga Viral , Adulto Jovem
3.
Front Immunol ; 12: 707355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276702

RESUMO

HIV-1 increases susceptibility to pulmonary infection and disease, suggesting pathogenesis in the lung. However, the lung immune environment during HIV infection remains poorly characterized. This study examined T cell activation and the cytokine milieu in paired bronchoalveolar lavage (BAL) and blood from 36 HIV-uninfected and 32 HIV-infected participants. Concentrations of 27 cytokines were measured by Luminex, and T cells were phenotyped by flow cytometry. Blood and BAL had distinct cytokine profiles (p=0.001). In plasma, concentrations of inflammatory cytokines like IFN-γ (p=0.004) and TNF-α (p=0.004) were elevated during HIV infection, as expected. Conversely, BAL cytokine concentrations were similar in HIV-infected and uninfected individuals, despite high BAL viral loads (VL; median 48,000 copies/ml epithelial lining fluid). HIV-infected individuals had greater numbers of T cells in BAL compared to uninfected individuals (p=0.007); and BAL VL positively associated with CD4+ and CD8+ T cell numbers (p=0.006 and p=0.0002, respectively) and CXCL10 concentrations (p=0.02). BAL T cells were highly activated in HIV-infected individuals, with nearly 2-3 fold greater frequencies of CD4+CD38+ (1.8-fold; p=0.007), CD4+CD38+HLA-DR+ (1.9-fold; p=0.0006), CD8+CD38+ (2.8-fold; p=0.0006), CD8+HLA-DR+ (2-fold; p=0.022) and CD8+CD38+HLA-DR+ (3.6-fold; p<0.0001) cells compared to HIV-uninfected individuals. Overall, this study demonstrates a clear disruption of the pulmonary immune environment during HIV infection, with readily detectable virus and activated T lymphocytes, which may be driven to accumulate by local chemokines.

4.
Eur Respir J ; 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140294

RESUMO

Rapid tests to evaluate SARS-CoV-2-specific T cell responses are urgently needed to decipher protective immunity and aid monitoring vaccine-induced immunity. Using a rapid whole blood assay requiring minimal amount of blood, we measured qualitatively and quantitatively SARS-CoV-2-specific CD4T cell responses in 31 healthcare workers, using flow cytometry. 100% of COVID-19 convalescent participants displayed a detectable SARS-CoV-2-specific CD4T cell response. SARS-CoV-2-responding cells were also detected in 40.9% of participants with no COVID-19-associated symptoms or who tested PCR negative. Phenotypic assessment indicated that, in COVID-19 convalescent participants, SARS-CoV-2 CD4 responses displayed an early differentiated memory phenotype with limited capacity to produce IFNÉ£. Conversely, in participants with no reported symptoms, SARS-CoV-2 CD4 responses were enriched in late differentiated cells, co-expressing IFNÉ£ and TNFα and also Granzyme B. This proof-of-concept study presents a scalable alternative to PBMC-based assays to enumerate and phenotype SARS-CoV-2-responding T cells, thus representing a practical tool to monitor adaptive immunity due to natural infection or vaccine trials.

5.
Clin Infect Dis ; 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181706

RESUMO

Understanding what shapes the latent HIV-1 reservoir is critical for developing strategies for cure. We measured the frequency of persistent HIV-1 infection after 5 years of suppressive antiretroviral therapy initiated during chronic infection. Pre-treatment CD8 + T-cell activation, nadir CD4 count, and CD4:CD8 ratio predicted reservoir size.

6.
J Clin Invest ; 131(12)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33945513

RESUMO

T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2-specific (SARS-CoV-2-specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non-COVID-19 patients. We showed that SARS-CoV-2-specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1-mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis-specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.


Assuntos
Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , Coinfecção/imunologia , HIV-1/imunologia , Mycobacterium tuberculosis/imunologia , SARS-CoV-2/imunologia , Tuberculose/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/patologia , COVID-19/patologia , Coinfecção/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tuberculose/patologia
7.
Mucosal Immunol ; 14(2): 491-499, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32678272

RESUMO

Recent data from mice and non-human primate models of tuberculosis suggested that CD153, a TNF super family member, plays an important role in Mycobacterium tuberculosis (Mtb) control. However, this molecule has not been comprehensively evaluated in humans. Here, we show that the proportion of Mtb-specific CD4 T cells expressing CD153 was significantly reduced in active TB patients compared to latently infected persons. Importantly, the CD153+ Mtb-specific CD4 response inversely correlated with lung bacterial load, inferred by Xpert cycle threshold, irrespective of HIV status. Antitubercular treatment partially restored CD153 expression on Mtb-specific CD4 T cells. This is the first report of a subset of Mtb-specific CD4 T cells showing strong negative correlation with bacterial burden. Building on substantial evidence from animal models implicating CD153 as a mediator of host protection, our findings suggest it may play a similar role in humans and its measurement may be useful to evaluate TB vaccine efficacy.

8.
medRxiv ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33173918

RESUMO

Rapid tests to evaluate SARS-CoV-2-specific T cell responses are urgently needed to decipher protective immunity and aid monitoring vaccine-induced immunity. Using a rapid whole blood assay requiring minimal amount of blood, we measured qualitatively and quantitatively SARS-CoV-2-specific CD4 T cell responses in 31 healthcare workers, using flow cytometry. 100% of COVID-19 convalescent participants displayed a detectable SARS-CoV-2-specific CD4 T cell response. SARS-CoV-2-responding cells were also detected in 40.9% of participants with no COVID-19-associated symptoms or who tested PCR negative. Phenotypic assessment indicated that, in COVID-19 convalescent participants, SARS-CoV-2 CD4 responses displayed an early differentiated memory phenotype with limited capacity to produce IFNγ. Conversely, in participants with no reported symptoms, SARS-CoV-2 CD4 responses were enriched in late differentiated cells, co-expressing IFNγ and TNFα and also Granzyme B. This proof of concept study presents a scalable alternative to PBMC-based assays to enumerate and phenotype SARS-CoV-2-responding T cells, thus representing a practical tool to monitor adaptive immunity in vaccine trials. Summary: In this proof of concept study, we show that SARS-CoV-2 T cell responses are easily detectable using a rapid whole blood assay requiring minimal blood volume. Such assay could represent a suitable tool to monitor adaptive immunity in vaccine trials.

9.
Clin Transl Immunology ; 9(9): e1176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005414

RESUMO

Objectives: The development of non-sputum-based assays for tuberculosis (TB) diagnosis and treatment monitoring is a key priority. Recent data indicate that whole blood-based assays to assess the phenotype of Mycobacterium tuberculosis (Mtb)-specific CD4 T cells hold promise for this purpose and require further investigation in well-characterised TB cohorts. In this study, we investigated the relationship between the phenotypic signature of Mtb-specific CD4 responses, TB disease extent and treatment response. Methods: Using flow cytometry, we measured the expression of phenotypic and functional markers (HLA-DR, CD27, CD153, KLRG1, IL-2, MIP-1ß, TNF-α and IFN-γ) on Mtb-specific CD4 T-cells in whole blood from 161 participants of varying TB and HIV status. TB disease extent was graded as a continuum using the Xpertct value, C-reactive protein, Timika radiographic score and monocyte/lymphocyte ratio. Results: The phenotypic profile of Mtb-specific CD4 T cells pre-anti-tubercular treatment (ATT) strongly correlated with disease extent, irrespective of HIV status. ATT associated with major changes in the phenotype of Mtb-specific CD4 T cells, with decreased expression of HLA-DR and increased CD27 and CD153 expression. Principal component analysis showed an almost complete separation between latent TB infection (LTBI) and active TB (aTB) pre-ATT groups, whereas the profile of the aTB post-ATT group overlapped with the LTBI group. However, in patients experiencing treatment failure or relapse, no significant changes were observed in Mtb-specific CD4 T-cell phenotype pre- and post-ATT. Conclusion: Whole blood-based assays of Mtb-specific CD4 T-cell activation and maturation markers can be used as non-sputum-based biomarkers of disease extent and treatment monitoring in TB, regardless of HIV-1 status.

10.
Sci Rep ; 10(1): 17438, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060706

RESUMO

Botrytis cinerea is a necrotic plant fungus that causes gray mold disease in over 200 crops, including grapevine. Due to its genetic plasticity, this fungus presents strong resistance to many fungicides. Thus, new strategies against B. cinerea are urgently needed. In this context, antimicrobial photodynamic treatment (APDT) was considered. APDT involves the use of a photosensitizer that generates reactive oxygen species upon illumination with white light. Tetra-4-sulfonatophenyl porphyrin tetra-ammonium (TPPS) was tested on B. cinerea using light. 1.5 µM TPPS completely inhibited mycelial growth. TPPS (12.5 µM) was tested on three grapevine clones from Chardonnay, Merlot and Sauvignon, grown in vitro for 2 months. Treated root apparatus of the three backgrounds increased thiol production as a molecular protection against photoactivated TPPS, leading to a normal phenotype as compared with control plantlets. Finally, 2-month-old grapevine leaves were infected with 4-day-old mycelium of B. cinerea pre-incubated or not with TPPS. The pre-treated mycelium was unable to infect the detached leaves of any of the three grapevine varieties after 72 h growth when subjected to a 16 h photoperiod, contrary to untreated mycelium. These results suggest a strong potential of photo-treatment against B. cinerea mycelium for future agricultural practices in vineyard or other cultures.


Assuntos
Botrytis/efeitos dos fármacos , Fungicidas Industriais/química , Controle de Pragas/métodos , Doenças das Plantas/microbiologia , Porfirinas/química , Vitis/microbiologia , Ânions , Farmacorresistência Fúngica , Luz , Folhas de Planta/microbiologia , Espécies Reativas de Oxigênio/metabolismo
11.
J Infect Dis ; 221(1): 162-167, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419285

RESUMO

The reconstitution of Mycobacterium tuberculosis antigen-specific CD4 T cells in a cohort of HIV-infected persons starting antiretroviral treatment (ART) in a high tuberculosis endemic area is described. Restoration of the antigen-specific CD4 T-cell subsets mirrored the overall CD4 T-cell compartment. Activation (assessed by HLA-DR expression) decreased during ART but remained elevated compared to HIV-uninfected persons. Despite known M. tuberculosis sensitization determined by interferon-γ release assay, 12/23 participants had no M. tuberculosis-specific CD4 T cells detectable by flow cytometry, combined with overall elevated T-cell activation and memory differentiation, suggesting heightened turnover. Our data suggest early ART initiation to maintain polyfunctional immune memory responses.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Adulto , Antígenos de Bactérias/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/metabolismo , Feminino , Citometria de Fluxo , Infecções por HIV/complicações , Antígenos HLA-DR/metabolismo , Humanos , Memória Imunológica , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Ativação Linfocitária , Masculino
12.
Biochemistry ; 58(16): 2188-2197, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30942568

RESUMO

In this study, our fundamental research interest was to understand how negatively charged porphyrins could interact with a plant cell wall and further act inside cells. Thus, three anionic porphyrins differing in their anionic external groups (carboxylates, sulfonates, and phosphonates) were tested. First, the tobacco cell wall was isolated to monitor in vitro its interactions with the three different anionic porphyrins. Unexpectedly, these negatively charged molecules were able to bind to the negatively charged cell wall probably by weak bonds such as hydrogen bonds and/or electrostatic interactions when the tetrapyrrolic core was protonated. Moreover, we showed that at the pH of spent culture medium (4.5), the neutrality of the carboxylated porphyrin (TPPC) facilitated its cell wall crossing while the diffusion of the two other sulfonated (TPPS) or phosphonated (TPPP) porphyrins that remained anionic was delayed. Once inside Tobacco Bright Yellow-2 (TBY-2) cells, TPPC induced higher levels of production of both H2O2 and malondialdehyde compared to TPPS after illumination. That result correlated well with strong cell death induction by photoactivated TPPC. Furthermore, reactive oxygen species-scavenging enzymes such as catalase, peroxidases, and superoxide dismutase were also strongly downmodulated in response to TPPC, while these enzymes were almost unchanged in response to photoactivated TPPS. To the best of our knowledge, this is the first study that took into account the whole story from interactions of porphyrins with a plant cell wall to their photodynamic activity inside the cells.


Assuntos
Ânions/química , Parede Celular/metabolismo , Fármacos Fotossensibilizantes/química , Porfirinas/química , Ânions/metabolismo , Sítios de Ligação , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Células Cultivadas , Ligação de Hidrogênio , Peróxido de Hidrogênio/metabolismo , Luz , Malondialdeído/metabolismo , Estrutura Molecular , Organofosfonatos/química , Organofosfonatos/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/metabolismo , Sulfonas/química , Sulfonas/metabolismo , Tabaco/citologia , Tabaco/efeitos dos fármacos , Tabaco/metabolismo
13.
PLoS One ; 13(12): e0209516, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30589870

RESUMO

HIV-1 co-infection is a leading cause of susceptibility to tuberculosis (TB), with the risk of TB being increased at all stages of HIV-1 infection. Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected individuals sensitised by Mycobacterium tuberculosis (Mtb) can thus help identify mechanisms of protection against TB. In order to understand ART-mediated prevention of TB in HIV-1 infected adults, we investigated the expression of 30 genes in whole blood from HIV-1 infected patients during the first 6 months of ART-induced immune reconstitution. The 30 selected genes were previously described to be differentially expressed between sorted Mtb specific central and effector memory CD4 T cells. HIV-1 infected persons sensitised by Mtb were recruited in Khayelitsha, South Africa, when initiating ART. RNA was extracted from whole blood at initiation and 1, 3 and 6 months of ART. qRT-PCR was used to determine gene expression and three reference 'housekeeping' genes were used to calculate the fold change in the expression of each gene relative to day 0 of ART. Results were assessed longitudinally. We observed a decrease in the expression of a number of genes at 6 months of ART, reflecting a decrease in immune activation. However, following correction for multiple comparisons and increasing CD4 counts, only the decrease in CD27 gene expression remained statistically significant. While not statistically significant, a number of genes also showed increased expression at various timepoints, illustrating the broad regeneration of the T cell pool in HIV-1 infected adults on ART. Our findings generate hypotheses underlying ART- induced protective immune reconstitution and may pave the way for future studies to evaluate ART mediated prevention of TB in HIV-1 infected persons.


Assuntos
Coinfecção , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Tuberculose/microbiologia , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Feminino , Perfilação da Expressão Gênica , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Imunização , Testes de Liberação de Interferon-gama , Masculino , Mycobacterium tuberculosis/imunologia , Resultado do Tratamento , Tuberculose/imunologia , Tuberculose/metabolismo , Carga Viral
14.
Nat Microbiol ; 3(11): 1198-1205, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30202016

RESUMO

Mycobacterium tuberculosis infection (Mtb) is the leading cause of death due to a single infectious agent and is among the top ten causes of all human deaths worldwide1. CD4 T cells are essential for resistance to Mtb infection, and for decades it has been thought that IFNγ production is the primary mechanism of CD4 T-cell-mediated protection2,3. However, IFNγ responses do not correlate with host protection, and several reports demonstrate that additional anti-tuberculosis CD4 T-cell effector functions remain unaccounted for4-8. Here we show that the tumour-necrosis factor (TNF) superfamily molecule CD153 (encoded by the gene Tnfsf8) is required for control of pulmonary Mtb infection by CD4 T cells. In Mtb-infected mice, CD153 expression is highest on Mtb-specific T helper 1 (TH1) cells in the lung tissue parenchyma, but its induction does not require TH1 cell polarization. CD153-deficient mice develop high pulmonary bacterial loads and succumb early to Mtb infection. Reconstitution of T-cell-deficient hosts with either Tnfsf8-/- or Ifng-/- CD4 T cells alone fails to rescue mice from early mortality, but reconstitution with a mixture of Tnfsf8-/- and Ifng-/- CD4 T cells provides similar protection as wild-type T cells. In Mtb-infected non-human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the airways compared to blood, and the frequency of Mtb-specific CD153-expressing CD4 T cells inversely correlates with bacterial loads in granulomas. In Mtb-infected humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells that are much more abundant in individuals with controlled latent Mtb infection compared to those with active tuberculosis. In all three species, Mtb-specific CD8 T cells did not upregulate CD153 following peptide stimulation. Thus, CD153 is a major immune mediator of host protection against pulmonary Mtb infection and CD4 T cells are one important source of this molecule.


Assuntos
Ligante CD30/genética , Resistência à Doença/genética , Expressão Gênica , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Animais , Carga Bacteriana , Ligante CD30/deficiência , Ligante CD30/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Modelos Animais de Doenças , Resistência à Doença/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Pulmão/imunologia , Pulmão/microbiologia , Camundongos , Mycobacterium tuberculosis/fisiologia , Primatas , Células Th1/imunologia , Células Th1/metabolismo , Tuberculose/microbiologia
15.
Front Plant Sci ; 9: 681, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29875786

RESUMO

In the 1970's, an unconventional stressful photodynamic treatment applied to plants was investigated in two directions. Exogenous photosensitizer treatment underlies direct photodynamic stress while treatment mediating endogenous photosensitizer over-accumulation pinpoints indirect photodynamic stress. For indirect photodynamic treatment, tetrapyrrole biosynthesis pathway was deregulated by 5-aminolevulenic acid or diphenyl ether. Overall, photodynamic stress involves the generation of high amount of reactive oxygen species leading to plant cell death. All these investigations were mainly performed to gain insight into new herbicide development but they were rapidly given up or limited due to the harmfulness of diphenyl ether and the high cost of 5-aminolevulinic acid treatment. Twenty years ago, plant photodynamic stress came back by way of crop transgenesis where for example protoporphyrin oxidases from human or bacteria were overexpressed. Such plants grew without dramatic effects of photodamage suggesting that plants tolerated induced photodynamic stress. In this review, we shed light on the occurrence of plant photodynamic stress and discuss challenging issues in the context of agriculture focusing on direct photodynamic modality. Indeed, we highlighted applications of exogenous PS especially porphyrins on plants, to further develop an emerged antimicrobial photodynamic treatment that could be a new strategy to kill plant pathogens without disturbing plant growth.

16.
Clin Immunol ; 195: 127-138, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29883708

RESUMO

HIV infection results in excessive T cell activation and dysfunction which may persist even during effective antiretroviral therapy (ART). The dynamics of immune 'deactivation' and extent to which T cell memory subsets normalize after ART are unclear. We longitudinally assessed the influence of 1 year of ART on the phenotype of T cells in HIV-infected African women, relative to matched HIV-uninfected women, using activation (CD38, HLA-DR) and differentiation markers (CD27, CD45RO). ART induced a substantial reduction in T cell activation, but remained higher than HIV-uninfected controls. ART largely normalized the distribution of CD4+ T cell memory subsets, while the distribution of CD8+ T cell memory subsets remained significantly skewed compared to HIV-uninfected individuals. Thus, there was a considerable but only partial reversal of T cell defects upon ART. Understanding T cell impairment may provide important insights into mechanisms of HIV pathogenesis in the era of ART.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Adulto , Anticorpos Antivirais/sangue , Terapia Antirretroviral de Alta Atividade , Diferenciação Celular , Feminino , Citometria de Fluxo , Infecções por HIV/tratamento farmacológico , Humanos , Memória Imunológica , Imunofenotipagem , Ativação Linfocitária , África do Sul , Carga Viral
17.
Annu Rev Immunol ; 36: 603-638, 2018 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-29490165

RESUMO

Globally, about 36.7 million people were living with HIV infection at the end of 2015. The most frequent infection co-occurring with HIV-1 is Mycobacterium tuberculosis-374,000 deaths per annum are attributable to HIV-tuberculosis, 75% of those occurring in Africa. HIV-1 infection increases the risk of tuberculosis by a factor of up to 26 and alters its clinical presentation, complicates diagnosis and treatment, and worsens outcome. Although HIV-1-induced depletion of CD4+ T cells underlies all these effects, more widespread immune deficits also contribute to susceptibility and pathogenesis. These defects present a challenge to understand and ameliorate, but also an opportunity to learn and optimize mechanisms that normally protect people against tuberculosis. The most effective means to prevent and ameliorate tuberculosis in HIV-1-infected people is antiretroviral therapy, but this may be complicated by pathological immune deterioration that in turn requires more effective host-directed anti-inflammatory therapies to be derived.


Assuntos
Coinfecção , Infecções por HIV/imunologia , HIV-1/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Animais , Terapia Antirretroviral de Alta Atividade , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Progressão da Doença , Variação Genética , Infecções por HIV/diagnóstico , Infecções por HIV/terapia , Infecções por HIV/virologia , HIV-1/genética , Humanos , Tuberculose/diagnóstico , Tuberculose/microbiologia , Tuberculose/terapia , Replicação Viral
18.
Physiol Plant ; 162(3): 379-390, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29111597

RESUMO

Antimicrobial photodynamic treatment (APDT) based on the use of a photosensitizer to produce reactive oxygen species (ROS) that induce cell death could be envisaged to fight against plant pathogens. For setting this strategy, we want to study how plants themselves respond to photodynamic treatment. In previous work we showed that tomato plantlets were able to resist photoactivated tetra (N-methylpyridyl) porphyrin (CP) or the zinc metalated form (CP-Zn). To enlarge our plant expertise related to exogenous porphyrins treatment and to further defend this approach, we studied how a weed like Arabidopsis thaliana responded to exogenous supply of anionic and cationic porphyrins. Both types of photosensitizers had no negative effect on seed germination and did not hamper the development etiolated Arabidopsis plantlet under dark conditions. Thus, post-emergence effects of porphyrin photoactivation on the development of 14 day-old in vitro Arabidopsis plantlet under light were observed. CP-Zn was the most efficient photosensitizer to kill Arabidopsis plantlets while anionic tetra (4-sulfonatophenyl) porphyrin only delayed their growth and development. Indeed only 7% of plantlets could be rescued after CP-Zn treatment. Furthermore, non-enzymatic and enzymatic defense components involved in detoxification of ROS generated by CP-Zn under illumination were downregulated or stable with the exception of sevenfold increase in proline content. As previously demonstrated in the literature for microbial agents and in the present work for Arabidopsis, CP-Zn was efficient enough to eradicate unwanted vegetation and plant pathogens without at the same time killing plants of agronomic interest such as tomato plantlets.


Assuntos
Arabidopsis/efeitos dos fármacos , Arabidopsis/efeitos da radiação , Luz , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Ânions/química , Antioxidantes/metabolismo , Arabidopsis/fisiologia , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Cátions/química , Germinação/efeitos dos fármacos , Germinação/efeitos da radiação , Malondialdeído/metabolismo , Fármacos Fotossensibilizantes/química , Proteínas de Plantas/metabolismo , Porfirinas/química , Espécies Reativas de Oxigênio/metabolismo , Sementes/efeitos dos fármacos , Sementes/fisiologia , Sementes/efeitos da radiação , Superóxido Dismutase/metabolismo , Zinco/química , Zinco/farmacologia
19.
J Infect Dis ; 216(12): 1550-1560, 2017 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-29029171

RESUMO

Human immunodeficiency virus type 1 (HIV) infection substantially increases the risk of developing tuberculosis. There is extensive depletion of Mycobacterium tuberculosis-specific CD4+ T cells in blood during early HIV infection, but little is known about responses in the lungs at this stage. Given that mucosal organs are a principal target for HIV-mediated CD4+ T-cell destruction, we investigated M. tuberculosis-specific responses in bronchoalveolar lavage (BAL) from persons with latent M. tuberculosis infection and untreated HIV coinfection with preserved CD4+ T-cell counts. M. tuberculosis-specific CD4+ T-cell cytokine (interferon γ, tumor necrosis factor α, and interleukin 2) responses were discordant in frequency and function between BAL and blood. Responses in BAL were 15-fold lower in HIV-infected persons as compared to uninfected persons (P = .048), whereas blood responses were 2-fold lower (P = .006). However, an increase in T cells in the airways in HIV-infected persons resulted in the overall number of M. tuberculosis-specific CD4+ T cells in BAL being similar. Our study highlights the important insights gained from studying M. tuberculosis immunity at the site of disease during HIV infection.


Assuntos
Sangue/imunologia , Linfócitos T CD4-Positivos/imunologia , Coinfecção/imunologia , Infecções por HIV/imunologia , Tuberculose Latente/imunologia , Pulmão/imunologia , Mycobacterium tuberculosis/imunologia , Adulto , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Infecções por HIV/complicações , Humanos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Tuberculose Latente/complicações , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
20.
J Immunol ; 2017 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-28794233

RESUMO

A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4+ T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4+ T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M.tuberculosis-specific MHC class II tetramers. We examined the phenotype as well as function of ex vivo M. tuberculosis-specific tetramer+CD4+ T cells using flow cytometry. The numbers of M. tuberculosis-specific tetramer+CD4+ T cells were relatively well maintained in HIV-infected persons with aTB, despite severe immunodeficiency. However, although HIV-uninfected persons with latent TB infection exhibited ex vivo M. tuberculosis-specific CD4+ T cells predominantly of a CXCR3+CCR6+CCR4- (Th1*) phenotype, aTB or HIV infection was associated with a contraction of this subset. Nevertheless, in individuals with aTB and/or HIV infection, circulating ex vivo M. tuberculosis-specific CD4+ T cells did not display defects in exhaustion or polyfunctionality compared with healthy HIV-uninfected individuals with latent TB infection. Collectively, these data suggest that increased susceptibility to TB disease could be related to a loss of circulating Th1* CD4+ T cells rather than major changes in the number or function of circulating CD4+ T cells.

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