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1.
Nat Commun ; 12(1): 1750, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741942

RESUMO

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Antiprotozoários/farmacologia , Epitopos/imunologia , Células Germinativas/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Adulto , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/química , Antígenos de Protozoários/imunologia , Sítios de Ligação , Células Cultivadas , Epitopos/química , Interações Hospedeiro-Parasita/efeitos dos fármacos , Interações Hospedeiro-Parasita/imunologia , Humanos , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/imunologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Mosquitos Vetores/parasitologia , Plasmodium falciparum/imunologia , Plasmodium falciparum/fisiologia , Conformação Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia
2.
Mol Immunol ; 132: 172-183, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33601226

RESUMO

The trypanosomatid pathogens Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei, currently grouped as TriTryps, have evolved through the time to overcome the upfront innate immune response and establish the infection in humans adapting many aspects of the parasite-cell host interaction. Extracellular vesicles (EVs) emerge as critical structures carrying different key molecules from parasites and target cells that interact continuously during infection. Current information regarding the structure and composition of these vesicles provide new insights into the primary role of TriTryps-EVs reviewed in this work. Expanding knowledge about these critical vesicular structures will promote advances in basic sciences and in translational applications controlling pathogenesis in the neglected tropical diseases caused by TriTryps.


Assuntos
Vesículas Extracelulares/imunologia , Leishmania major/imunologia , Infecções por Protozoários/imunologia , Trypanosoma brucei brucei/imunologia , Trypanosoma cruzi/imunologia , Animais , Vesículas Extracelulares/parasitologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Imunidade Inata/imunologia , Infecções por Protozoários/parasitologia
3.
Int J Mol Sci ; 22(2)2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33477394

RESUMO

Protease inhibitors (PIs) are ubiquitous regulatory proteins present in all kingdoms. They play crucial tasks in controlling biological processes directed by proteases which, if not tightly regulated, can damage the host organism. PIs can be classified according to their targeted proteases or their mechanism of action. The functions of many PIs have now been characterized and are showing clinical relevance for the treatment of human diseases such as arthritis, hepatitis, cancer, AIDS, and cardiovascular diseases, amongst others. Other PIs have potential use in agriculture as insecticides, anti-fungal, and antibacterial agents. PIs from tick salivary glands are special due to their pharmacological properties and their high specificity, selectivity, and affinity to their target proteases at the tick-host interface. In this review, we discuss the structure and function of PIs in general and those PI superfamilies abundant in tick salivary glands to illustrate their possible practical applications. In doing so, we describe tick salivary PIs that are showing promise as drug candidates, highlighting the most promising ones tested in vivo and which are now progressing to preclinical and clinical trials.


Assuntos
Inibidores de Proteases/isolamento & purificação , Inibidores de Proteases/uso terapêutico , Saliva/metabolismo , Animais , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Humanos , Saliva/química , Glândulas Salivares/metabolismo , Carrapatos/metabolismo , Transcriptoma/genética
4.
Trends Parasitol ; 37(2): 165-175, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33502317

RESUMO

The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, an infection that manifests as colitis and, in some cases, liver abscess. A better understanding of host protective factors is key to developing an effective remedy. Recently, significant advances have been made in understanding the mechanisms of MUC2 production by goblet cells upon amebic infection, regulation of antimicrobial peptide production by Paneth cells, the interaction of commensal microbiota with immune stimulation, and host genetics in conferring protection from amebiasis. In addition to host pathways that may serve as potential therapeutic targets, significant progress has also been made with respect to development of a vaccine against amebiasis. Here, we aim to highlight the current understanding and knowledge gaps critically.


Assuntos
Entamebíase/imunologia , Interações Hospedeiro-Parasita/imunologia , Entamoeba histolytica , Entamebíase/genética , Entamebíase/parasitologia , Entamebíase/prevenção & controle , Células Caliciformes/imunologia , Células Caliciformes/parasitologia , Humanos , Mucina-2/imunologia , Celulas de Paneth/imunologia , Proteínas Citotóxicas Formadoras de Poros/imunologia , Vacinas Protozoárias
5.
Viruses ; 12(12)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339349

RESUMO

Here we have studied the impact of lice (Lepeophtheirus salmonis) infestation of donor fish on the ability of isolated peripheral blood monocytes (PMBCs) to control the replication of salmonid alphavirus (SAV) ex vivo. PMBC were collected by Percoll gradients at eight and nine weeks post copepodid infestation of Atlantic salmon post smolt. Uninfested fish were controls. PBMCs were then infected ex vivo with SAV (subtype 3), and samples were collected for analysis at two, four, and six days post virus infection. Virus titer in the supernatant was assayed in CHH-1 cells, and in addition, the relative expression of the virus structural protein E2 and selected host antiviral genes, IRF9, ISG15, Mx, and IFIT5, were assayed using real-time PCR. Significantly higher virus replication was detected in cells collected from lice-infested fish compared to controls. Higher virus titer coincided with an inability to upregulate the expression of different immune genes, IFIT5, IRF9, and Mx. These findings point towards compromised ability of PMBCs from lice-infested fish to control virus replication, and, to our knowledge, is the first report showing the direct effect of lice infestation on the interplay between viruses and immune cells. There is a possible impact on the dynamic spread of viral diseases in the aquatic environment.


Assuntos
Alphavirus/fisiologia , Ectoparasitoses/veterinária , Doenças dos Peixes/imunologia , Interações Hospedeiro-Parasita/imunologia , Monócitos/imunologia , Salmo salar/virologia , Replicação Viral , Animais , Células Cultivadas , Ectoparasitoses/imunologia , Salmo salar/imunologia
6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(8): 755-759, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32958133

RESUMO

Ureaplasma urealyticum and Ureaplasma parvum are the most common Ureaplasma species causing repeated or persistent infection of the urogenital tract. The host can mobilize innate and adaptive immunity to defend and eliminate pathogens. However, under certain conditions, the host's immune protection cannot completely clear Ureaplasma species. Ureaplasma species have evolved a complex and sophisticated escape mechanism in the long-term defense against host immune protection. This article summarizes the research progress on Ureaplasma species' immune escape mechanism from several aspects such as evading host autophagy mechanism, antagonizing host nutritional immunity and regulating host cell gene expression.


Assuntos
Interações Hospedeiro-Parasita , Evasão da Resposta Imune , Infecções por Ureaplasma , Ureaplasma , Interações Hospedeiro-Parasita/imunologia , Humanos , Evasão da Resposta Imune/imunologia , Pesquisa/tendências , Ureaplasma/imunologia , Infecções por Ureaplasma/imunologia
7.
PLoS Negl Trop Dis ; 14(9): e0008601, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886659

RESUMO

Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease.


Assuntos
Interações Hospedeiro-Parasita/imunologia , Sarcoptes scabiei/imunologia , Escabiose/veterinária , Sus scrofa/imunologia , Sus scrofa/parasitologia , Animais , Citocinas/genética , Citocinas/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Imunomodulação/imunologia , Escabiose/imunologia , Escabiose/patologia , Pele/imunologia , Pele/parasitologia , Pele/patologia , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/parasitologia , Células Th17/imunologia , Células Th2/imunologia , Transcriptoma/genética
8.
Parasitol Res ; 119(10): 3165-3180, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32789534

RESUMO

Parasitic diseases affect more than one billion people worldwide, and most of them are chronic conditions in which the treatment and prevention are difficult. The appearance of granulomas, defined as organized and compact structures of macrophages and other immune cells, during various parasitic diseases is frequent, since these structures will only form when individual immune cells do not control the invading agent. Th2-typering various parasitic diseases are frequent, since these structures will only form when individual immune cells do not control the invading agent. The characterization of granulomas in different parasitic diseases, as well as recent findings in this field, is discussed in this review, in order to understand the significance of the granuloma and its modulation in the host-parasite interaction and in the immune, pathological, and parasitological aspects of this interaction. The parasitic granulomatous diseases granulomatous amebic encephalitis, toxoplasmosis, leishmaniasis, neurocysticercosis, and schistosomiasis mansoni are discussed as well as the mechanistic and dynamical aspects of the infectious granulomas.


Assuntos
Granuloma/imunologia , Granuloma/patologia , Macrófagos/imunologia , Neurocisticercose/imunologia , Esquistossomose mansoni/imunologia , Toxoplasmose/imunologia , Animais , Granuloma/parasitologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Macrófagos/patologia , Neurocisticercose/patologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/patologia , Taenia solium/imunologia , Toxoplasma/imunologia , Toxoplasmose/patologia
9.
Trends Parasitol ; 36(9): 773-784, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32736985

RESUMO

Emerging evidence suggests that the DNA-sensing pathway plays a crucial role in innate immunity against multiple diseases, especially infectious diseases. Cyclic GMP-AMP synthase (cGAS), as a DNA sensor, and stimulator of interferon (IFN) genes (STING), as an adaptor protein, are the central components that link DNA sensing to immunologic functions - including, but not limited to, the type I IFN response. Recently, a series of studies have revealed that genomic DNA from protozoan parasites triggers the cGAS-STING pathway, and these studies identified the positive and negative regulators that modulate the signaling in parasite infection. Here, we summarize current understanding of the critical functions and potential applications of the cGAS-STING axis in parasitic diseases, specifically those caused by malaria parasites.


Assuntos
Interações Hospedeiro-Parasita/imunologia , Malária/imunologia , Malária/parasitologia , Proteínas de Membrana/metabolismo , Nucleotidiltransferases/metabolismo , Plasmodium/genética , Plasmodium/imunologia , Animais , DNA de Protozoário/genética , DNA de Protozoário/imunologia , Humanos , Transdução de Sinais/genética
10.
Trends Parasitol ; 36(9): 761-772, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32713764

RESUMO

Gastrointestinal helminth infection still constitutes a major public health issue, particularly in the developing world. As these parasites can undergo a large part of their lifecycle within the intestinal tract the host has developed various structural and cellular specializations at the epithelial barrier to contend with infection. Detailed characterization of these cells will provide important insights about their contributions to the protective responses mediated against helminths. Here, we discuss how key components of the intestinal epithelium may function to limit the initial establishment of helminths, and how these cells are altered during an active response to infection.


Assuntos
Helmintíase/imunologia , Interações Hospedeiro-Parasita/imunologia , Mucosa Intestinal/inervação , Mucosa Intestinal/parasitologia , Animais , Helmintíase/parasitologia , Helmintos/imunologia , Humanos
12.
Trends Parasitol ; 36(8): 668-676, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32540194

RESUMO

Understanding the origin of sex differences in lifespan and aging patterns remains a salient challenge in both biogerontology and evolutionary biology. Different factors have been studied but the potential influence of pathogens has never been investigated. Sex differences, especially in hormones and resource allocation, generate a differential response to pathogens and thereby shape sex differences in lifespan or aging. We provide an integrative framework linking host pathogenic environment with both sex-specific selections on immune performance and mortality trajectories. We propose future directions to fill existing knowledge gaps about mechanisms that link sex differences, not only to exposition and sensitivity to pathogens, but also to mortality patterns, whilst emphasizing the urgent need to consider the role of sex in medicine.


Assuntos
Envelhecimento/fisiologia , Interações Hospedeiro-Parasita/fisiologia , Mamíferos/parasitologia , Doenças Parasitárias/epidemiologia , Envelhecimento/imunologia , Animais , Evolução Biológica , Interações Hospedeiro-Parasita/imunologia , Humanos , Longevidade , Mamíferos/imunologia , Doenças Parasitárias/parasitologia , Fatores Sexuais
13.
PLoS Negl Trop Dis ; 14(6): e0008358, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32589656

RESUMO

Antibody-mediated parasite killing is considered the most effective host immune response against extracellular trypanosome parasites. However, due to host-parasite co-evolution pressure, these parasites have "learned" how to hijack the host immune system via the development of immune evasion strategies. Hereby they prevent elimination and promote transmission. In the past, our group has shown that African trypanosome parasites are able to "shut down" the host B cell compartment, via the abolishment of the homeostatic B cell compartment. In line with this, we have reported that trypanosome infections result in detrimental outcomes on auto-reactive and cancer B cells. To unravel the immune mechanisms involved in these processes we adopted here a well-defined B cell vaccine model, i.e. the thymo-dependent hapten-carrier NP-CGG (4-Hydroxy-3-nitrophenylacetyl-Chicken Gamma Globulin) emulsified in Alum adjuvant. Results show that T. brucei infections abrogate the circulating titres of vaccine-induced CGG-specific as well as NP-specific IgG1+ antibodies, a hallmark of memory B cell responses in this model. This happens independently of their affinity and IFNÉ£ signalling. Next, we demonstrate that T. brucei infections also induce a decrease of anti-NP IgG3+ antibodies induced by the administration of NP coupled to Ficoll, a thymo-independent antigen. Confirming the non-specificity of the infection-associated immunopathology, this report also shows that trypanosome infections abolish vaccine-induced memory response against malaria parasite in BALB/c mice. Together, these data indicates that T. brucei infections impair every stages of B cell development, including effector plasma B cells, independently of their specificity and affinity as well as the host genetic background.


Assuntos
Subpopulações de Linfócitos B/imunologia , Plasmócitos/imunologia , Tripanossomíase Africana/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Linfócitos B/imunologia , Modelos Animais de Doenças , Feminino , Patrimônio Genético , Interações Hospedeiro-Parasita/imunologia , Evasão da Resposta Imune , Imunidade Humoral , Imunoglobulina G , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Vacinas Protozoárias/imunologia , Trypanosoma brucei brucei
14.
PLoS Pathog ; 16(5): e1008478, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32437438

RESUMO

Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.


Assuntos
Adaptação Fisiológica/imunologia , Antifúngicos/uso terapêutico , Candida/fisiologia , Candidíase , Farmacorresistência Fúngica/imunologia , Interações Hospedeiro-Parasita/imunologia , Candidíase/tratamento farmacológico , Candidíase/imunologia , Candidíase/patologia , Humanos
15.
Int J Nanomedicine ; 15: 2957-2969, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425527

RESUMO

Experimental and epidemiological evidence shows that parasites, particularly helminths, play a central role in balancing the host immunity. It was demonstrated that parasites can modulate immune responses via their excretory/secretory (ES) and some specific proteins. Extracellular vesicles (EVs) are nano-scale particles that are released from eukaryotic and prokaryotic cells. EVs in parasitological studies have been mostly employed for immunotherapy of autoimmune diseases, vaccination, and diagnosis. EVs can carry virulence factors and play a central role in the development of parasites in host cells. These molecules can manipulate the immune responses through transcriptional changes. Moreover, EVs derived from helminths modulate the immune system via provoking anti-inflammatory cytokines. On the other hand, EVs from parasite protozoa can induce efficient immunity, that makes them useful for probable next-generation vaccines. In addition, it seems that EVs from parasites may provide new diagnostic approaches for parasitic infections. In the current study, we reviewed isolation methods, functions, and applications of parasite's EVs in immunotherapy, vaccination, and diagnosis.


Assuntos
Vesículas Extracelulares/metabolismo , Interações Hospedeiro-Parasita/imunologia , Imunoterapia/métodos , Parasitos/citologia , Animais , Doenças Autoimunes/terapia , Citocinas/metabolismo , Vesículas Extracelulares/química , Vesículas Extracelulares/classificação , Humanos , Imunidade , Parasitos/patogenicidade , Doenças Parasitárias/diagnóstico , Vacinação , Vacinas/imunologia , Fatores de Virulência/metabolismo
16.
Nat Immunol ; 21(7): 790-801, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32424361

RESUMO

Plasmodium parasite-specific antibodies are critical for protection against malaria, yet the development of long-lived and effective humoral immunity against Plasmodium takes many years and multiple rounds of infection and cure. Here, we report that the rapid development of short-lived plasmablasts during experimental malaria unexpectedly hindered parasite control by impeding germinal center responses. Metabolic hyperactivity of plasmablasts resulted in nutrient deprivation of the germinal center reaction, limiting the generation of memory B cell and long-lived plasma cell responses. Therapeutic administration of a single amino acid to experimentally infected mice was sufficient to overcome the metabolic constraints imposed by plasmablasts and enhanced parasite clearance and the formation of protective humoral immune memory responses. Thus, our studies not only challenge the current model describing the role and function of blood-stage Plasmodium-induced plasmablasts but they also reveal new targets and strategies to improve anti-Plasmodium humoral immunity.


Assuntos
Imunidade Humoral , Malária/imunologia , Plasmócitos/metabolismo , Plasmodium falciparum/imunologia , Adolescente , Adulto , Aminoácidos/administração & dosagem , Aminoácidos/metabolismo , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Anticorpos Antiprotozoários/metabolismo , Antimaláricos/administração & dosagem , DNA de Protozoário/isolamento & purificação , Modelos Animais de Doenças , Centro Germinativo/citologia , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Interações Hospedeiro-Parasita/imunologia , Humanos , Malária/sangue , Malária/tratamento farmacológico , Malária/parasitologia , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Nutrientes/metabolismo , Plasmócitos/imunologia , Plasmócitos/parasitologia , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Estudo de Prova de Conceito , Adulto Jovem
17.
Parasite Immunol ; 42(8): e12731, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32403169

RESUMO

The salmon louse Lepeophtheirus salmonis (Lsal) is an ectoparasitic copepod that exerts immunomodulatory and physiological effects on its host Atlantic salmon. Over 30 years of research on louse biology, control, host responses and the host-parasite relationship has provided a plethora of information on the intricacies of host resistance and parasite adaptation. Atlantic salmon exhibit temporal and spatial impairment of the immune system and wound healing ability during infection. This immunosuppression may render Atlantic salmon less tolerant to stress and other confounders associated with current management strategies. Contrasting susceptibility of salmonid hosts exists, and early pro-inflammatory Th1 type responses are associated with resistance. Rapid cellular responses to larvae appear to tip the balance of the host-parasite relationship in favour of the host, preventing severe immune-physiological impacts of the more invasive adults. Immunological, transcriptomic, genomic and proteomic evidence suggests pathological impacts occur in susceptible hosts through modulation of host immunity and physiology via pharmacologically active molecules. Co-evolutionary and farming selection pressures may have incurred preference of Atlantic salmon as a host for Lsal reflected in their interactome. Here, we review host-parasite interactions at the primary attachment/feeding site, and the complex life stage-dependent molecular mechanisms employed to subvert host physiology and immune responses.


Assuntos
Copépodes/imunologia , Doenças dos Peixes/parasitologia , Interações Hospedeiro-Parasita/imunologia , Salmão/imunologia , Salmão/parasitologia , Animais , Suscetibilidade a Doenças/imunologia , Doenças dos Peixes/imunologia , Tolerância Imunológica/imunologia , Larva/imunologia , Proteômica , Salmão/genética , Células Th1/imunologia , Transcriptoma , Cicatrização/imunologia
18.
Trends Parasitol ; 36(5): 447-458, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32298632

RESUMO

Estimation of Plasmodium vivax biomass based on circulating biomarkers indicates the existence of a predominant biomass outside of the circulation that is not captured by peripheral parasitemia, in particular in patients with complicated outcomes. A series of recent studies have suggested that the hematopoietic niche of the bone marrow (BM) is a major reservoir for parasite replication and the development of transmission stages. However, significant knowledge gaps remain in our understanding of host-parasite interactions, pathophysiology, and the implications for treatment and diagnosis of such a reservoir. Here, we discuss the current status of this emerging research field in the context of P. vivax.


Assuntos
Interações Hospedeiro-Parasita/imunologia , Malária Vivax/imunologia , Malária Vivax/parasitologia , Biomassa , Medula Óssea/imunologia , Medula Óssea/parasitologia , Hematopoese/imunologia , Humanos , Malária Vivax/transmissão , Plasmodium vivax/fisiologia , Pesquisa/tendências , Reticulócitos/imunologia , Reticulócitos/parasitologia
19.
BMC Evol Biol ; 20(1): 43, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299345

RESUMO

BACKGROUND: Parasites may mediate the success of biological invasions through their effect on host fitness and thus, on host population growth and stability. However, a release from the pressure of parasites is strongly related to the genetic differentiation of the host. In invasive host populations, the number of available genetic variants, allowing them to 'fight' the infection, are likely to be influenced by founder events and genetic drift. The level standing genetic variation of invasive populations may be crucial in successfully adapting to new environments and resisting diseases. We studied invasive populations of raccoon that experienced a random reduction in genetic diversity during the establishment and evaluated the relationship between host immune genetic diversity and intestinal parasites infection. RESULTS: We distinguished two different genetic clusters that are characterized by different sets of functionally relevant MHC-DRB alleles. Both clusters were characterized by considerably different allele-parasite associations and different levels of parasite infection. The specific resistance MHC-DRB alleles explained the lower prevalence of Digenea parasites. An increased infection intensity was related to the presence of two MHC-DRB alleles. One of these alleles significantly decreased in frequency over time, causing a decrease of Digenea abundance in raccoons in consecutive years. CONCLUSIONS: Our findings suggest that intestinal parasites can exert selective pressure on an invasive host with lowered levels of immune genetic diversity and contribute to promoting local adaptation over time. The random genetic drift that created the two different genetic clusters in the invasive raccoon range imposed completely different MHC-parasite associations, strongly associated with the infection status of populations. Our findings underline the role of standing genetic variation in shaping host-parasite relationships and provide empirical support that functional genetic variation may be, at least partly, responsible for differences in the success of invasive populations.


Assuntos
Variação Genética , Interações Hospedeiro-Parasita , Espécies Introduzidas , Guaxinins/genética , Guaxinins/imunologia , Alelos , Animais , Interações Hospedeiro-Parasita/imunologia , Intestinos/parasitologia , Família Multigênica , Parasitos/fisiologia , Seleção Genética
20.
Parasit Vectors ; 13(1): 154, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228657

RESUMO

BACKGROUND: Methyltransferases (MTFs) are broad range of enzymes, which are ubiquitously expressed in diverse organisms ranging from bacteria to animals. MTFs proteins have been associated with various biological/cellular processes including transcriptional regulation, subcellular protein and RNA localization, signal transduction and DNA-damage repair. However, the role of MTFs in immune mechanism during host-parasite interaction has not been addressed yet. RESULTS: An open reading frame (764 bp) of methyltransferase-type 12 gene of H. contortus denoted as HcMTF-12, was successfully cloned using reverse transcriptase-polymerase chain reaction (RT-PCR) followed by prokaryotic expression in Escherichia coli BL21 (DE3 strain). The recombinant HcMTF-12 protein (rHcMTF-12) was about 47 kDa along with a fusion vector protein of 18 kDa. Immunoblot results identified the native protein MTF-12 with antibodies produced in rats against rHcMT-12, whereas rHcMTF-12 protein was recognized with sera of goat experimentally infected with H. contortus. Immunohistochemical analysis revealed that the native MTF-12 protein was mainly located in the periphery (cuticle) of parasite sections as well as within the pharynx and intestinal region. An immunofluorescence assay validated that rHcMTF-12 attached to the surface of goat PBMCs. Furthermore, the cytokines transcription of IL-2, IFN-γ and IL-4 transcripts of PBMCs incubated with rHcMTF-12 were enhanced in a dose-dependent manner. The secretion of TGF-ß1 and IL-10 was significantly decreased. However, IL-6 production was not significantly different as compared to the control groups. Moreover, the migration activity and nitric oxide (NO) production by PBMCs were induced considerably, whereas the proliferation of PBMCs cells was negatively affected when incubated with the rHcMTF-12 protein. CONCLUSIONS: Our findings suggest that HcMTF-12 significantly mediated the functions of PBMCs, and it might be a potential candidate for therapeutic interventions against haemonchosis.


Assuntos
Cabras/parasitologia , Haemonchus/enzimologia , Haemonchus/genética , Leucócitos Mononucleares/imunologia , Metiltransferases/genética , Metiltransferases/imunologia , Metiltransferases/isolamento & purificação , Animais , Anticorpos Anti-Helmínticos/sangue , Proliferação de Células , Clonagem Molecular , Citocinas/metabolismo , Modelos Animais de Doenças , Escherichia coli/genética , Feminino , Regulação da Expressão Gênica , Hemoncose/parasitologia , Hemoncose/veterinária , Proteínas de Helminto/genética , Interações Hospedeiro-Parasita/imunologia , Masculino , Metiltransferases/metabolismo , Óxido Nítrico/metabolismo , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Alinhamento de Sequência , Análise de Sequência de Proteína
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