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1.
PLoS Pathog ; 20(8): e1012479, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39178325

RESUMO

Alveolar echinococcosis (AE) is a highly lethal helminth infection. Current chemotherapeutic strategies for AE primarily involve the use of benzimidazoles (BZs) such as mebendazole (MDZ) and albendazole (ABZ), which exhibit limited efficacy. In a previous study, the vaccine of recombinant Echinococcus granulosus P29 (rEgP29) showed significant immunoprotection against E. granulosus in both mice and sheep. In the current study, we utilized hybridoma technology to generate five monoclonal antibodies (mAbs) against P29, among which 4G10F4 mAb exhibited the highest antigen-specific binding capacity. This mAb was selected for further investigation of anti-AE therapy, both in vivo and in vitro. In vitro, 4G10F4 inhibited a noteworthy inhibition of E. multilocularis protoscoleces and primary cells viability through complement-dependent cytotoxicity (CDC) mechanism. In vivo, two experiments were conducted. In the first experiment, mice were intraperitoneally injected with Em protoscoleces, and subsequently treated with 4G10F4 mAb (2.5/5/10 mg/kg) at 12 weeks postinfection once per week for 8 times via tail vein injection. Mice that were treated with 4G10F4 mAb only in dosage of 5mg/kg exhibited a significant lower mean parasite burden (0.89±0.97 g) compared to isotype mAb treated control mice (2.21±1.30 g). In the second experiment, mice were infected through hepatic portal vein and treated with 4G10F4 mAb (5mg/kg) at one week after surgery once per week for 8 times. The numbers of hepatic metacestode lesions of the 4G10F4 treatment group were significantly lower in comparison to the isotype control group. Pathological analysis revealed severe disruption of the inner structure of the metacestode in both experiments, particularly affecting the germinal and laminated layers, resulting in the transformation into infertile vesicles after treatment with 4G10F4. In addition, the safety of 4G10F4 for AE treatment was confirmed through assessment of mouse weight and evaluation of liver and kidney function. This study presents antigen-specific monoclonal antibody immunotherapy as a promising therapeutic approach against E. multilocularis induced AE.


Assuntos
Anticorpos Monoclonais , Equinococose , Animais , Equinococose/tratamento farmacológico , Equinococose/imunologia , Anticorpos Monoclonais/farmacologia , Camundongos , Proteínas de Helminto/imunologia , Proteínas de Helminto/farmacologia , Camundongos Endogâmicos BALB C , Echinococcus multilocularis/imunologia , Echinococcus multilocularis/efeitos dos fármacos , Feminino , Echinococcus granulosus/imunologia , Ovinos , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia
2.
J Infect Dis ; 230(4): 1023-1032, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-38942608

RESUMO

Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole-proteome differential screening method, we identified Schistosoma japonicum helminth defense molecule 1 (SjHDM-1) as a target of antibodies expressed by S. japonicum-resistant but not S. japonicum-susceptible individuals. In a longitudinal cohort study (n = 644) conducted in a S. japonicum-endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 immunoglobulin G had higher levels of C-reactive protein than those with low anti-SjHDM-1. High anti-SjHDM-1 immunoglobulin G responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (weight-for-age and height-for-age z scores) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity rates.


Assuntos
Anticorpos Anti-Helmínticos , Inflamação , Estado Nutricional , Esquistossomose Japônica , Humanos , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Animais , Feminino , Esquistossomose Japônica/imunologia , Masculino , Filipinas/epidemiologia , Inflamação/imunologia , Estudos Longitudinais , Adulto , Schistosoma japonicum/imunologia , Adolescente , Proteínas de Helminto/imunologia , Adulto Jovem , Criança , Pessoa de Meia-Idade , Hepatomegalia/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia
3.
Microb Pathog ; 195: 106847, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127365

RESUMO

Schistosomiasis caused by Schistosoma japonicum (S. japonicum) is a major public health problem in the Philippines, China and Indonesia. In this study, the immunopotentiator CpG-ODN was encapsulated within chitosan nanoparticles (Chi NPs) to create a combination adjuvant (Chi-CpG NP). This approach was employed to enhance the immunogenicity of 26 kDa glutathione S-transferase (Sj26GST) from S. japonicum through intranasal immunization. The results demonstrated higher levels of specific anti-Sj26GST antibodies and Sj26GST-specific splenocyte proliferation compared to mice that were immunized with Sj26GST + Chi-CpG NP. Cytokine analysis of splenocytes revealed that the Sj26GST + Chi-CpG NP induced a slight Th1-biased immune response, with increased production of IFN-γ by CD4+ T-cells in the spleen. Subsequently, mice were intradermally inoculated with 1 × 107 organisms in the Coeliac cavity. The bacterial organ burden detected in the liver of immunized mice suggested that Sj26GST + Chi-CpG NP enhances protective immunity to inhibit S. japonicum colonization. Therefore, Sj26GST + Chi-CpG NP vaccination enhances Sj26GST-specific immunogenicity and provides protection against S. japonicum.


Assuntos
Adjuvantes Imunológicos , Anticorpos Anti-Helmínticos , Quitosana , Glutationa Transferase , Imunização , Nanopartículas , Oligodesoxirribonucleotídeos , Schistosoma japonicum , Esquistossomose Japônica , Baço , Animais , Schistosoma japonicum/imunologia , Schistosoma japonicum/enzimologia , Glutationa Transferase/imunologia , Glutationa Transferase/genética , Camundongos , Esquistossomose Japônica/prevenção & controle , Esquistossomose Japônica/imunologia , Adjuvantes Imunológicos/administração & dosagem , Quitosana/administração & dosagem , Anticorpos Anti-Helmínticos/imunologia , Feminino , Baço/imunologia , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/imunologia , Citocinas/metabolismo , Interferon gama/metabolismo , Linfócitos T CD4-Positivos/imunologia , Administração Intranasal , Camundongos Endogâmicos BALB C , Fígado/parasitologia , Fígado/imunologia , Células Th1/imunologia , Modelos Animais de Doenças , Vacinação , Antígenos de Helmintos/imunologia , Antígenos de Helmintos/administração & dosagem
4.
Parasitol Res ; 123(4): 196, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662084

RESUMO

Many pathogens are related to carcinogenesis. Chronic inflammation, as a result of persistent infection, leads to DNA damage, higher expression of oncogenes, decreased apoptosis and immunosuppression, which are some of the reasons for cancer induction. Among parasites, Schistosoma, Opistorchis and Clonorchis are recognised as infectious agents which contribute to cancer. A relationship between Anisakis and cancer was hypothesised because cellular responses to Anisakis products could result in inflammation and DNA damage. Previous research has shown a decrease in CD8+ γδ T-cells and an increase in αß and γδ T-cell apoptosis in colon cancer (CC) samples. Ninety-two CC patients and 60 healthy subjects were recruited. γδ and αß T-cells were analysed, and their apoptosis was evaluated. Anti-Anisakis antibodies were tested in sera from CC patients and controls. Anti-Anisakis IgG, IgM, IgA and IgE antibodies were significantly higher in CC patients. A significant increase in anti-Anisakis IgA levels was observed in patients with angiolymphatic invasion. The number of all γδ T-cells, as well as CD3+ CD4+ αß T-cells, was significantly lower in CC patients. The apoptosis of all T-cells was significantly increased in patients with CC. We observed a significantly higher percentage of anti-Anisakis IgE positive patients having a deficit of CD3+ γδ T-cells. Our results suggest a relationship between Anisakis and CC.


Assuntos
Anisakis , Anticorpos Anti-Helmínticos , Neoplasias do Colo , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Feminino , Neoplasias do Colo/imunologia , Neoplasias do Colo/parasitologia , Idoso , Animais , Anisakis/imunologia , Adulto , Apoptose , Idoso de 80 Anos ou mais , Subpopulações de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia
5.
PLoS Pathog ; 16(3): e1008243, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32203551

RESUMO

Trichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children's educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T-cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule T-cell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). Bone marrow-derived dendritic cells and bone marrow-derived macrophages responded in vitro to VLPs irrespective of whether the VLP also included T-cell epitopes. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T-cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine.


Assuntos
Epitopos de Linfócito T/imunologia , Tricuríase/prevenção & controle , Trichuris/imunologia , Vacinas/imunologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Simulação por Computador , Células Dendríticas/imunologia , Epitopos de Linfócito T/administração & dosagem , Epitopos de Linfócito T/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Imunogenicidade da Vacina , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tricuríase/imunologia , Tricuríase/parasitologia , Trichuris/genética , Vacinas/administração & dosagem , Vacinas/genética
6.
J Infect Dis ; 223(7): 1265-1274, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33606021

RESUMO

Schistosomiasis remains a leading cause of chronic morbidity in endemic regions despite decades of widespread mass chemotherapy with praziquantel. Using our whole proteome differential screening approach, and plasma and epidemiologic data from a longitudinal cohort of individuals living in a Schistosoma japonicum-endemic region of the Philippines, we interrogated the parasite proteome to identify novel vaccine candidates for Schistosoma japonicum. We identified 16 parasite genes which encoded proteins that were recognized by immunoglobulin G or immunoglobulin E antibodies in the plasma of individuals who had developed resistance to reinfection, but were not recognized by antibodies in the plasma of individuals who remained susceptible to reinfection. Antibody levels to Sj6-8 and Sj4-1 measured in the entire cohort (N = 505) 1 month after praziquantel treatment were associated with significantly decreased risk of reinfection and lower intensity of reinfection over 18 months of follow-up.


Assuntos
Anticorpos Anti-Helmínticos , Schistosoma japonicum , Esquistossomose Japônica , Vacinas , Animais , Anticorpos Anti-Helmínticos/imunologia , Resistência à Doença , Humanos , Recidiva Local de Neoplasia , Praziquantel/uso terapêutico , Proteoma , Reinfecção/prevenção & controle , Schistosoma japonicum/genética , Esquistossomose Japônica/prevenção & controle
7.
PLoS Pathog ; 15(11): e1007926, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31730667

RESUMO

The majority of experiments investigating the immune response to gastrointestinal helminth infection use a single bolus infection. However, in situ individuals are repeatedly infected with low doses. Therefore, to model natural infection, mice were repeatedly infected (trickle infection) with low doses of Trichuris muris. Trickle infection resulted in the slow acquisition of immunity reflected by a gradual increase in worm burden followed by partial expulsion. Flow cytometry revealed that the CD4+ T cell response shifted from Th1 dominated to Th2 dominated, which coincided with an increase in Type 2 cytokines. The development of resistance following trickle infection was associated with increased worm expulsion effector mechanisms including goblet cell hyperplasia, Muc5ac production and increased epithelial cell turn over. Depletion of CD4+ T cells reversed resistance confirming their importance in protective immunity following trickle infection. In contrast, depletion of group 2 innate lymphoid cells did not alter protective immunity. T. muris trickle infection resulted in a dysbiotic mircrobiota which began to recover alpha diversity following the development of resistance. These data establish trickle infection as a robust and informative model for analysis of immunity to chronic intestinal helminth infection more akin to that observed under natural infection conditions and confirms the importance of CD4+ T cell adaptive immunity in host protection.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Hipersensibilidade/imunologia , Imunidade Inata/imunologia , Intestinos/imunologia , Pulmão/imunologia , Tricuríase/imunologia , Trichuris/imunologia , Imunidade Adaptativa , Animais , Anticorpos Anti-Helmínticos/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/parasitologia , Hipersensibilidade/parasitologia , Intestinos/parasitologia , Intestinos/patologia , Pulmão/parasitologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Th2/imunologia , Células Th2/parasitologia , Tricuríase/sangue , Tricuríase/parasitologia
8.
PLoS Pathog ; 15(9): e1007924, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31487324

RESUMO

Parasitic helminths evade, skew and dampen human immune responses through numerous mechanisms. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we analyzed the effects that soluble egg antigen (SEA) from Schistosoma mansoni had on modulating HIV-1 infection and cytokine/chemokine production in vitro. We determined that SEA, specifically through kappa-5, can potently bind to DC-SIGN and thereby blocks DC-SIGN mediated HIV-1 trans-infection (p<0.05) whilst not interfering with cis-infection. DCs exposed to SEA whilst maturing under Th2 promoting conditions, will upon co-culture with naïve T-cells induce a T-cell population that was less susceptible to HIV-1 R5 infection (p<0.05) compared to DCs unexposed to SEA, whereas HIV-1 X4 virus infection was unaffected. This was not observed for DCs exposed to SEA while maturing under Th1 or Th1/Th2 (Tmix) promoting conditions. All T-cell populations induced by SEA exposed DCs demonstrate a reduced capacity to produce IFN-γ and MIP-1ß. The infection profile of T-cells infected with HIV-1 R5 was not associated with down-modulation of CCR5 cell surface expression. We further show that DCs maturing under Tmix conditions exposed to plant recombinant omega-1 protein (rω-1), which demonstrates similar functions to natural ω-1, induced T-cell populations that were less sensitive for HIV-1 R5 infection (p<0.05), but not for X4 virus infection. This inhibition associated again with a reduction in IFN-γ and MIP-1ß expression, but additionally correlated with reduced CCR5 expression. We have shown that SEA parasite antigens and more specifically rω-1 can modulate HIV-1 infectivity with the potential to influence disease course in co-infected individuals.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Proteínas do Ovo/imunologia , Infecções por HIV/metabolismo , Animais , Anticorpos Anti-Helmínticos/metabolismo , Antígenos de Helmintos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Proteínas do Ovo/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Humanos , Ativação Linfocitária , Receptores CCR5/metabolismo , Schistosoma mansoni/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Replicação Viral/imunologia
9.
Trop Med Int Health ; 26(9): 1098-1109, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107115

RESUMO

OBJECTIVES: We measured the production of cytokines, chemokines and antibodies involved in allergic responses and sCD23 levels during Schistosoma mansoni infection. METHODS: Individuals (n = 164) were selected using the ISAAC questionnaire and parasitological exams. The subjects were divided as follows: those infected individuals with allergy-related symptoms (A-I), those with allergy-related symptoms only (A-NI); those only infected (NA-I); and those non-infected individuals without allergy-related symptoms (NA-NI). We used supernatants from cell culture (mitogenic stimulation) to measure cytokine and chemokine levels using cytometric bead arrays. Serum levels of anti-Ascaris lumbricoides (Asc) and anti-Blomia tropicalis IgE were measured using ImmunoCAP, and sCD23 was measured using ELISA. RESULTS: Schistosoma mansoni infection was associated with a lower risk of allergy-related symptoms. In A-I, there were higher levels of TNF-α, IL-10, IL-6, IFN-γ and CXCL8 than in NA-NI group, with TNF-α and IL-6 also at higher levels compared to A-NI group. Levels of IL-6, CXCL8, total and anti-Asc IgE, as well as the numbers of eosinophils, were higher in NA-I than in NA-NI, and the antibodies were also lower in A-NI than in NA-I group. In AI and NA-I, there was less production of CCL2 than in NA-NI. There were no differences in the levels of IL-2, IL-4, IL-17, CCL5, sCD23 and anti-Blomia IgE. CONCLUSIONS: Patients with allergy-related symptoms and infected (simultaneously) had higher levels of IL-10; due to the infection, there was increased production of IL-6 and CXCL8 and less CCL2. These data may characterize deviation to Th1 or attenuation of the Th2 response in allergy sufferers in areas endemic for schistosomiasis.


Assuntos
Anticorpos/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Hipersensibilidade Respiratória/parasitologia , Esquistossomose mansoni/imunologia , Adolescente , Adulto , Animais , Anticorpos/sangue , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Brasil/epidemiologia , Quimiocina CCL2/imunologia , Quimiocinas/sangue , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Humanos , Imunoglobulina E , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Trop Med Int Health ; 26(12): 1634-1644, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510662

RESUMO

OBJECTIVES: The aims of the study were two-fold: (1) antigen (Ag) preparation and evaluation of three antigens of Gnathostoma spinigerum infective larvae (GsL3), crude somatic antigen (CSAg), excretory-secretory antigen (ESAg) and partially purified antigens (namely P1Ag, P2Ag and P3Ag) to differentiate IgE, IgG, IgG1-4 and IgM for human gnathostomiasis diagnosis; and (2) application of the selected ELISA for following up stored sera of patients treated with ivermectin (IVM) and albendazole (ABZ). METHODS: Different antigens were analysed by antibodies of gnathostomiasis cases, other parasite infections and healthy controls using indirect ELISA to differentiate IgE, IgG, IgG1-4 and IgM. Then, prominent antigen and immunoglobulin were used in antibody predictions of gnathostomiasis cases treated with albendazole or ivermectin. RESULTS: Sensitivity of all evaluated ELISAs: IgM-, IgG-, IgG1- and IgG4-ELISA, was 100%. IgM-ELISA with CSAg and P3Ag exhibited the highest specificity of 99%. IgG-ELISA with P2Ag resulted in the highest specificity of 92.3%. IgG1-ELISA with P2Ag and P3Ag showed excellent results with 100% specificity. Finally, P2Ag evaluated IgG1 of the followed-up cases with ABZ and IVM. Decreasing antibody IgG1 levels were mostly found in both treatments at Month 9 and long follow-up was over 12 months. A Gnathostoma worm was extracted from each two treated patients. CONCLUSIONS: Using IgG1-ELISA against P2Ag and P3Ag gave excellent results with 100% sensitivity and specificity. These tests can be an alternative to immunoblotting for gnathostomiasis. IgG1 decreased at least 9 months in most cases, so long-term treatment should be performed over 1 year.


Assuntos
Antígenos de Helmintos/imunologia , Gnathostoma/imunologia , Gnatostomíase/sangue , Gnatostomíase/diagnóstico , Testes Imunológicos/métodos , Albendazol/uso terapêutico , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Antiparasitários/uso terapêutico , Gnatostomíase/tratamento farmacológico , Gnatostomíase/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Ivermectina/uso terapêutico , Larva/imunologia , Sensibilidade e Especificidade
11.
Parasite Immunol ; 43(2): e12798, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33012113

RESUMO

Hookworm infection is considered the most prevalent human soil-transmitted helminth infection affecting approximately 500 million people and accounting for 3.2 million disability-adjusted life years lost annually. As with many other neglected tropical diseases, no international surveillance mechanisms that show accurate data on the prevalence of hookworm infection are in place, thus hindering strategies to control parasite transmission. In this review, we unravel the current knowledge in immunopathology and immunoregulation of hookworm infection and present discoveries in drug therapies based on the capability of hookworms to regulate inflammation to treat allergic, inflammatory and metabolic diseases. Additionally, we highlight potential vaccine development and treatments and propose avenues for further inquiry.


Assuntos
Ancylostomatoidea/patogenicidade , Infecções por Uncinaria/imunologia , Infecções por Uncinaria/terapia , Animais , Anticorpos Anti-Helmínticos/imunologia , Interações Hospedeiro-Parasita , Humanos , Imunidade Celular , Imunomodulação , Masculino , Prevalência , Solo/parasitologia , Vacinas
12.
Parasite Immunol ; 43(3): e12802, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33098129

RESUMO

Polyreactive antibodies (pAb) bind to a broad range of unrelated structures, providing hosts with functional components able to rapidly recognize and protect against different pathogens. However, their roles against helminth parasites are still unexplored. Here, pAb profiles were analysed in cystic echinococcosis (CE), a zoonosis caused by the cestode Echinococcus granulosus sensu lato. Levels of anti-DNP (2,4-dinitrophenyl-hapten) antibodies were measured as a surrogate parameter of pAb in different biological settings. Firstly, levels of serum and peritoneal pAb were measured during early experimental secondary CE, using both high (Balb/c) and low (C57Bl/6) susceptible mouse strains. Serum pAb mostly differed in normal mice, being pAb levels of IgG subclasses with poor anti-parasite activities predominant in Balb/c animals. Conversely, peritoneal pAb isotypes/subclasses with efficient anti-parasite activities predominated in normal and infected C57Bl/6 mice. Secondly, sera from potentially resistant patients, susceptible individuals and healthy donors were analysed, showing higher pAb levels of the IgA and IgG-particularly IgG1-isotypes in potentially resistant individuals compared to control groups. Finally, since remarkable differences were observed in pAb profiles according to the intrinsic host susceptibility to the infection, we proposed here that pAb might be considered as potential humoral biomarkers for host resistance to CE.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Equinococose/imunologia , Echinococcus granulosus/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Biomarcadores , Suscetibilidade a Doenças/imunologia , Equinococose/parasitologia , Imunidade Humoral , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
13.
Exp Parasitol ; 221: 108049, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33307097

RESUMO

Globally, ascariasis ranks as the second leading intestinal helminth infection. However, progress in developing better control strategies, such as vaccines, remains slow-paced. This study aims to measure antibody production and parasite load in male BALB/c mice immunized with crude Ascaris suum intestinal tract homogenate. Thirty-two (32) mice were randomized into: (1) unvaccinated, uninfected (UU); (2) unvaccinated, infected (UI); (3) vaccinated, uninfected (VU); and (4) vaccinated, infected (VI) groups. A 100-µL vaccine containing 50 µg of homogenized A. suum intestines and Complete Freund's Adjuvant (1:1) were introduced intraperitoneally. Immunizations were done on days 0, 10, and 20. Oral gavage with 1000 embryonated eggs was done on day 30. Blood was obtained at day 40. To measure serum IgG levels, indirect ELISA was done. Microtiter plates were coated with 100 µg larval homogenate, and HRP-conjugated anti-mouse IgG was used as secondary antibody. Parasite load was measured in lung and liver tissues. Tukey's HSD of signal to cut-off ratios of absorbance readings obtained in indirect ELISA procedure for the 1:200 serum dilution showed statistically significant difference between the UU and VI (p = 0.026) as well as between UI and VI (p = 0.003) groups. No statistically significant difference in parasite load was observed in the lungs (p = 0.074), liver (p = 0.130), and both lungs and liver (p = 0.101). Immunization elicited a significant larva-directed IgG production. However, there is no significant difference in parasite loads in either lung or liver tissues across all treatment groups as the larval counts obtained from the study were very low and may not be indicative of the actual parasite load in mice.


Assuntos
Anticorpos Anti-Helmínticos/biossíntese , Antígenos de Helmintos/biossíntese , Ascaris suum/imunologia , Imunoglobulina G/biossíntese , Análise de Variância , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Imunização/métodos , Imunoglobulina G/imunologia , Intestinos/parasitologia , Larva/imunologia , Fígado/parasitologia , Pulmão/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Distribuição Aleatória
14.
Exp Parasitol ; 231: 108173, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34742714

RESUMO

Extracellular vesicles (EVs) from parasitic helminths play an important role in immunomodulation. However, EVs are little studied in the important parasite Fasciola gigantica. Here the ability of EVs from F. gigantica to induce cellular response to stress (reactive oxygen species generation, autophage and DNA damage response) in human intrahepatic biliary epithelial cells (HIBEC) was investigated. F. gigantica-derived EVs were isolated by ultracentrifugation, and identified with transmission electron microscopy, nanoparticle size analysis and parasite-derived EV markers. Internalization of EVs by HIBEC was determined by confocal immunofluorescence microscopy and flow cytometry. ROS levels in HIBEC were detected by molecular probing. EVs-induced autophagy and DNA-damaging effects were determined by evaluating expression levels of light chain 3B protein (LC3B), phosphor- H2A.X and phosphor-Chk1, respectively. Results revealed that EVs with sizes predominately ranging from 39 to 110 nm in diameter were abundant in adult F. gigantica and contained the parasite-derived marker proteins enolase and 14-3-3, and EVs were internalized by HIBEC. Further, uptake of EVs into HIBEC was associated with increased levels of reactive oxygen species, LC3Ⅱ, phosphor-H2A.X and phosphor-Chk1, suggesting EVs are likely to induce autophagy and DNA damage & repair processes. These results indicate F. gigantica EVs are associated with modulations of host cell responses and have a potential important role in the host-parasite interactions.


Assuntos
Vesículas Extracelulares/fisiologia , Fasciola/fisiologia , Imunomodulação/fisiologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Anticorpos Anti-Helmínticos/isolamento & purificação , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Autofagia/fisiologia , Western Blotting , Búfalos/parasitologia , Linhagem Celular , Vesículas Extracelulares/parasitologia , Fasciola/ultraestrutura , Citometria de Fluxo , Interações Hospedeiro-Parasita , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Fígado/parasitologia , Microscopia Confocal , Microscopia de Fluorescência , Coelhos , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo
15.
J Infect Dis ; 221(11): 1805-1815, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-31201416

RESUMO

BACKGROUND: Serological assessments for human onchocerciasis are based on IgG4 reactivity against the OV-16 antigen, with sensitivities of 60-80%. We have previously identified 7 novel proteins that could improve serodiagnosis. METHODS: IgG4 responses to these 7 proteins were assessed by luciferase immunoprecipitation (LIPS) and enzyme-linked immunosorbent (ELISA) immunoassays. RESULTS: OVOC10469 and OVOC3261 were identified as the most promising candidates by IgG4-based immunoassays with sensitivities of 53% for rOVOC10469 and 78% for rOVOC3261 while specificity for each was >99%. These 2 antigens in combination with OV-16 increased the sensitivity for patent infections to 94%. The kinetics of appearance of these IgG4 responses based on experimentally infected non-human primates indicated that they were microfilarial- driven. Further, the IgG4 responses to both OVOC10469 and OVOC3261 (as well as to OV-16) drop significantly (p<0.05) following successful treatment for onchocerciasis. A prototype lateral flow rapid diagnostic test to detect IgG4 to both Ov-16 and OVOC3261 was developed and tested demonstrating an overall 94% sensitivity. CONCLUSION: The combined use of rOVOC3261 with OV-16 improved serologic assessment of O. volvulus infection, a current unmet need toward the goal of elimination of transmission of O. volvulus.


Assuntos
Antígenos de Helmintos/imunologia , Onchocerca volvulus/isolamento & purificação , Oncocercose/diagnóstico , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/sangue , Microfilárias/imunologia , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Pan troglodytes , Primatas/imunologia , Sensibilidade e Especificidade
16.
Parasite Immunol ; 42(7): e12717, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32249432

RESUMO

Macrophages, the major population of tissue-resident mononuclear phagocytes, contribute significantly to the immune response during helminth infection. Alternatively activated macrophages (AAM) are induced early in the anti-helminth response following tissue insult and parasite recognition, amplifying the early type 2 immune cascade initiated by epithelial cells and ILC2s, and subsequently driving parasite expulsion. AAM also contribute to functional alterations in tissues infiltrated with helminth larvae, mediating both tissue repair and inflammation. Their activation is amplified and occurs more rapidly following reinfection, where they can play a dual role in trapping tissue migratory larvae and preventing or resolving the associated inflammation and damage. In this review, we will address both the known and emerging roles of tissue macrophages during helminth infection, in addition to considering both outstanding research questions and new therapeutic strategies.


Assuntos
Imunidade Inata/imunologia , Macrófagos/imunologia , Infecções por Strongylida/imunologia , Estrongilídios/imunologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Arginase/imunologia , Quitinases/imunologia , Inflamação/parasitologia , Contagem de Leucócitos , Linfócitos/imunologia , Resistina/imunologia
17.
Parasite Immunol ; 42(11): e12777, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32681576

RESUMO

AIM: Identification of a 29 kDa heat stress protein in filarial parasite Setaria cervi and evaluation of its diagnostic potential against lymphatic filariasis. METHODS AND RESULTS: The Heat shock proteins (HSPs) were induced in filarial parasite S cervi by incubated at 42°C for 2 hours. The 10% SDS-PAGE of cytosolic extract showed several over-expressed bands. The MALDI-LC/MS analysis of 29 kDa band showed 100% similarity with Bm14-3-3 like protein 2. Multiple sequence alignment of Bm14-3-3 like protein 2 sequence with W bancrofti, Caenorhabditis elegans; Loa loa and Homo sapiens showed 100%, 86%, 83% and 78%, sequence similarity respectively. The antigenic efficacy of Sc14-3-3 protein was evaluated with different filarial sera using ELISA which showed cross-reactivity in order to Endemic Normal (EN) < Microfilaraemic (MF) < Chronic(CH) with IgG1 and EN < CH < MF in IgG4 ELISA. IgG1- and IgG4-specific immunoblotting with CH and MF sera further explicated its specific antigenic cross-reactivity. CONCLUSION: A 29 kDa heat shock protein of S cervi was identified as 14-3-3 protein having 100% homology to human filarial parasite B malayi. It showed strong reactivity with IgG1 and IgG4 subclass antibodies of W bancrofti-infected human sera suggesting that 14-3-3 protein could be used as a vaccine/ diagnostic marker.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Filariose Linfática/diagnóstico , Proteínas de Choque Térmico/imunologia , Imunoglobulina G/imunologia , Setaria (Nematoide)/imunologia , Wuchereria bancrofti/imunologia , Sequência de Aminoácidos , Animais , Biomarcadores/análise , Reações Cruzadas , Filariose Linfática/imunologia , Filariose Linfática/parasitologia , Feminino , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Helminto/genética , Proteínas de Helminto/imunologia , Proteínas de Helminto/metabolismo , Humanos , Alinhamento de Sequência , Setaria (Nematoide)/genética
18.
Parasite Immunol ; 42(3): e12693, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31880816

RESUMO

AIMS: Schistosomes infect approximately 250 million people worldwide. To date, there is no effective vaccine available for the prevention of schistosome infection in endemic regions. There remains a need to develop means to confer long-term protection of individuals against reinfection. In this study, an annexin, namely annexin B30, which is highly expressed in the tegument of Schistosoma mansoni was selected to evaluate its immunogenicity and protective efficacy in a mouse model. METHODS AND RESULTS: Bioinformatics analysis showed that there were three potential linear B-cell epitopes and four conformational B-cell epitopes predicted from annexin B30, respectively. Full-length annexin B30 was cloned and expressed in Escherichia coli BL21(DE3). In the presence of adjuvants, the soluble recombinant protein was evaluated for its protective efficacy in two independent vaccine trials. Immunization of CBA mice with recombinant annexin B30 formulated either in alum only or alum/CpG induced a mixed Th1/Th2 cytokine profile but no significant protection against schistosome infection was detected. CONCLUSION: Recombinant annexin B30 did not confer significant protection against the parasite. The molecule may not be suitable for vaccine development. However, it could be an ideal biomarker recommended for immunodiagnostics development.


Assuntos
Anexinas/imunologia , Antígenos de Helmintos/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Adjuvantes Imunológicos , Animais , Anexinas/administração & dosagem , Anexinas/análise , Anticorpos Anti-Helmínticos/imunologia , Formação de Anticorpos , Feminino , Camundongos , Camundongos Endogâmicos CBA , Proteínas Recombinantes/imunologia , Schistosoma mansoni/química , Esquistossomose mansoni/diagnóstico , Vacinas/imunologia
19.
Parasitology ; 147(13): 1480-1487, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32729450

RESUMO

The gastrointestinal nematode Heligmosomoides polygyrus bakeri shows enhanced survival in mice with colitis. As the antibody response plays an important role in antiparasitic immunity, antibodies against male and female L4 H. polygyrus were examined in mice with and without colitis. Levels of specific antibodies in the mucosa and serum were determined by enzyme-linked immunosorbent assay and immunogenic proteins of male and female parasites were identified using 2D electrophoresis and mass spectrometry. The function of identified proteins was explored with Blast2Go. Nematodes in mice with colitis induced higher levels of specific immunoglobulin G (IgG1) and IgA, a lower level of IgE in the small intestine and a higher level of IgE in serum against female L4. Infected mice with colitis recognized 12 proteins in male L4 and 10 in female L4. Most of the recognized proteins from male L4 were intermediate filament proteins, whereas the proteins from female L4 were primarily actins and galectins. Nematodes from mice with colitis were immunogenically different from nematodes from control mice. This phenomenon gives new insights into helminth therapy as well as host-parasite interactions.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Colite/imunologia , Proteínas de Helminto/imunologia , Nematospiroides dubius/fisiologia , Proteoma/imunologia , Infecções por Strongylida/imunologia , Animais , Colite/parasitologia , Feminino , Intestinos/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Strongylida/parasitologia
20.
Exp Parasitol ; 219: 108029, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33096112

RESUMO

Echinococcus granulosus is a worldwide zoonotic infection that causes human cystic echinococcosis (CE) or hydatid disease. The present study describes the isolation and production of a monoclonal antibody against recombinant AgB protein using the developed Human AntibodY Disease ENhanced (HAYDEN)-Filariasis library. The DNA sequences of the isolated clones were analyzed, followed by gene analysis and binding assays. Clone E1 showed a full-length sequence and represents the IgHV5-LV3 antibody gene family. The antibody protein yield was satisfactory, and it reacted specifically against rAgB. The novel E1 protein is potentially useful for the development of an antigen detection assay for CE. The ability of the Brugia malayi immune antibody library to isolate antibodies against Echinococcus granulosus antigens highlights the broad coverage of immune antibody libraries.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Anticorpos Monoclonais/isolamento & purificação , Brugia Malayi/imunologia , Echinococcus granulosus/imunologia , Lipoproteínas/imunologia , Animais , Anticorpos Monoclonais/imunologia , Sequência de Bases , Western Blotting , Brugia Malayi/genética , Equinococose/diagnóstico , Echinococcus granulosus/genética , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Humanos , Lipoproteínas/genética
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