RESUMEN
Immunosuppressed patients, particularly transplant recipients, can develop severe strongyloidiasis. This study aimed to detect anti-Strongyloides IgG antibodies in a panel of sera from liver transplant patients. Two techniques were used: ELISA as the initial screening test and Western blotting as a confirmatory test. ELISA reactivity of 10.9% (32/294) was observed. The 40-30 kDa fraction was recognised in 93.7% (30/32) of the patients, resulting in a positivity rate of 10.2%. These data highlight the importance of serological screening for Strongyloides stercoralis infection in liver transplant recipients.
Asunto(s)
Anticuerpos Antihelmínticos , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , Trasplante de Hígado , Strongyloides stercoralis , Estrongiloidiasis , Receptores de Trasplantes , Humanos , Estrongiloidiasis/diagnóstico , Estrongiloidiasis/inmunología , Estrongiloidiasis/sangre , Anticuerpos Antihelmínticos/sangre , Animales , Strongyloides stercoralis/inmunología , Inmunoglobulina G/sangre , Western Blotting , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Femenino , Adulto , Enfermedades Desatendidas/diagnóstico , Enfermedades Desatendidas/epidemiología , Enfermedades Desatendidas/inmunología , Huésped Inmunocomprometido , AncianoRESUMEN
The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-ß and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni, which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity.
Asunto(s)
Eosinófilos/inmunología , Inmunidad/inmunología , Hepatopatías/inmunología , Hígado/inmunología , Enfermedades Desatendidas/inmunología , Esquistosomiasis mansoni/inmunología , Animales , Citocinas/inmunología , Modelos Animales de Enfermedad , Eosinófilos/parasitología , Femenino , Fibrosis/inmunología , Fibrosis/parasitología , Granuloma/inmunología , Granuloma/parasitología , Intestinos/inmunología , Intestinos/parasitología , Hígado/parasitología , Hepatopatías/parasitología , Ratones , Ratones Endogámicos BALB C , Enfermedades Desatendidas/parasitologíaRESUMEN
Non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in immune cells development and function. Their expression is altered in different physiological and disease conditions, hence making them attractive targets for the understanding of disease etiology and the development of adjunctive control strategies, especially within the current context of mitigated success of control measures deployed to eradicate these diseases. In this review, we summarize our current understanding of the role of ncRNAs in the etiology and control of major human tropical diseases including tuberculosis, HIV/AIDS and malaria, as well as neglected tropical diseases including leishmaniasis, African trypanosomiasis and leprosy. We highlight that several ncRNAs are involved at different stages of development of these diseases, for example miR-26-5p, miR-132-3p, miR-155-5p, miR-29-3p, miR-21-5p, miR-27b-3p, miR-99b-5p, miR-125-5p, miR-146a-5p, miR-223-3p, miR-20b-5p, miR-142-3p, miR-27a-5p, miR-144-5p, miR-889-5p and miR-582-5p in tuberculosis; miR-873, MALAT1, HEAL, LINC01426, LINC00173, NEAT1, NRON, GAS5 and lincRNA-p21 in HIV/AIDS; miR-451a, miR-let-7b and miR-106b in malaria; miR-210, miR-30A-5P, miR-294, miR-721 and lncRNA 7SL RNA in leishmaniasis; and miR-21, miR-181a, miR-146a in leprosy. We further report that several ncRNAs were investigated as diseases biomarkers and a number of them showed good potential for disease diagnosis, including miR-769-5p, miR-320a, miR-22-3p, miR-423-5p, miR-17-5p, miR-20b-5p and lncRNA LOC152742 in tuberculosis; miR-146b-5p, miR-223, miR-150, miR-16, miR-191 and lncRNA NEAT1 in HIV/AIDS; miR-451 and miR-16 in malaria; miR-361-3p, miR-193b, miR-671, lncRNA 7SL in leishmaniasis; miR-101, miR-196b, miR-27b and miR-29c in leprosy. Furthermore, some ncRNAs have emerged as potential therapeutic targets, some of which include lncRNAs NEAT1, NEAT2 and lnr6RNA, 152742 in tuberculosis; MALAT1, HEAL, SAF, lincRNA-p21, NEAT1, GAS5, NRON, LINC00173 in HIV/AIDS; miRNA-146a in malaria. Finally, miR-135 and miR-126 were proposed as potential targets for the development of therapeutic vaccine against leishmaniasis. We also identify and discuss knowledge gaps that warrant for increased research work. These include investigation of the role of ncRNAs in the etiology of African trypanosomiasis and the assessment of the diagnostic potential of ncRNAs for malaria, and African trypanosomiasis. The potential targeting of ncRNAs for adjunctive therapy against tuberculosis, leishmaniasis, African trypanosomiasis and leprosy, as well as their targeting in vaccine development against tuberculosis, HIV/AIDS, malaria, African trypanosomiasis and leprosy are also new avenues to explore.
Asunto(s)
MicroARNs/inmunología , Enfermedades Desatendidas , ARN Largo no Codificante/inmunología , Regulación hacia Arriba/inmunología , Desarrollo de Vacunas , Proliferación Celular , Humanos , Enfermedades Desatendidas/inmunología , Enfermedades Desatendidas/prevención & controlRESUMEN
The leishmanin skin test (LST) has been used for decades to detect exposure and immunity to the parasite Leishmania, the causative agent of the neglected tropical disease leishmaniasis. In the LST, Leishmania antigen (leishmanin) is intradermally injected into the forearm. In an individual who has been previously infected, a delayed-type hypersensitivity (DTH) reaction results in a measurable induration at the site of the injection, indicating that previous exposure to Leishmania has resulted in the development of cell-mediated immunity. LST positivity is associated with long-lasting protective immunity against reinfection, most notably as reported for visceral leishmaniasis (VL). Despite efforts over the past few decades, leishmanin antigen is no longer produced under good manufacturing practice (GMP) conditions anywhere in the world. Consequently, the use of the LST in epidemiological studies has declined in favor of serological and molecular tests. In this review, we provide a historical overview of the LST and justification for the reintroduction of leishmanin. A GMP-grade leishmanin can be used to detect immunity in vivo by the LST and can be investigated for use in an interferon-γ release assay (IGRA), which may serve as an in vitro version of the LST. The LST will be a valuable tool for surveillance and epidemiological studies in support of the VL elimination programs and as a surrogate marker of immunity in vaccine clinical trials. METHODS: A review of the literature was conducted using PubMed as the primary database, with MeSH terms "leishmanin skin test" OR "Montenegro test" OR "Montenegro skin test." Articles written in English that describe the history or standardization of leishmanin, the use of leishmanin in an IGRA, or the use of the LST in epidemiological studies or vaccine trials were prioritized in our appraisal of the literature.
Asunto(s)
Antígenos de Protozoos/análisis , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/diagnóstico , Enfermedades Desatendidas/diagnóstico , Pruebas Cutáneas/métodos , Animales , Humanos , Inmunidad Celular , Leishmania/inmunología , Leishmania/fisiología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Enfermedades Desatendidas/inmunología , Enfermedades Desatendidas/parasitologíaRESUMEN
The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.
Asunto(s)
Susceptibilidad a Enfermedades , Esquistosomiasis Japónica/etiología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Ubiquitina Tiolesterasa/genética , Animales , Citocinas/sangre , Citocinas/metabolismo , Femenino , Factores de Transcripción Forkhead/metabolismo , Predisposición Genética a la Enfermedad , Inmunofenotipificación , Hígado/inmunología , Hígado/parasitología , Hígado/patología , Ratones , Ratones Noqueados , Enfermedades Desatendidas/etiología , Enfermedades Desatendidas/inmunología , Bazo/inmunología , Bazo/parasitología , Bazo/patologíaRESUMEN
Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The development of a vaccine that reduces the intensity of infection and maintains lower morbidity should be the primary target for infection control. Previously, our group demonstrated that immunization with crude Ascaris antigens in mice induced an IgG-mediated protective response with significant worm reduction. Here, we aimed to develop a multipeptide chimera vaccine based on conserved B-cell epitopes predicted from 17 common helminth proteomes using a bioinformatics algorithm. More than 480 B-cell epitopes were identified that are conserved in all 17 helminths. The Ascaris-specific epitopes were selected based on their reactivity to the pooled sera of mice immunized with Ascaris crude antigens or infected three times with A. suum infective eggs. The top 35 peptides with the strongest reactivity to Ascaris immune serum were selected to construct a chimeric antigen connected in sequence based on conformation. This chimera, called ASCVac-1, was produced as a soluble recombinant protein in an Escherichia coli expression system and, formulated with MPLA, was used to immunize mice. Mice immunized with ASCVac-1/MPLA showed around 50% reduced larvae production in the lungs after being challenged with A. suum infective eggs, along with significantly reduced inflammation and lung tissue/function damage. The reduced parasite count and pathology in infected lungs were associated with strong Th2 immune responses characterized by the high titers of antigen-specific IgG and its subclasses (IgG1, IgG2a, and IgG3) in the sera and significantly increased IL-4, IL-5, IL-13 levels in lung tissues. The reduced IL-33 titers and stimulated eosinophils were also observed in lung tissues and may also contribute to the ASCVac-1-induced protection. Taken together, the preclinical trial with ASCVac-1 chimera in a mouse model demonstrated its significant vaccine efficacy associated with strong IgG-based Th2 responses, without IgE induction, thus reducing the risk of an allergic response. All results suggest that the multiepitope-based ASCVac-1 chimera is a promising vaccine candidate against Ascaris sp. infections.
Asunto(s)
Antígenos Helmínticos/administración & dosificación , Ascariasis/prevención & control , Ascaris suum/inmunología , Enfermedades Desatendidas/prevención & control , Vacunas Antiprotozoos/administración & dosificación , Animales , Antígenos Helmínticos/inmunología , Ascariasis/inmunología , Ascariasis/parasitología , Ascariasis/patología , Ascaris suum/aislamiento & purificación , Femenino , Humanos , Pulmón/inmunología , Pulmón/parasitología , Pulmón/patología , Ratones , Enfermedades Desatendidas/inmunología , Enfermedades Desatendidas/parasitología , Enfermedades Desatendidas/patología , Vacunas Antiprotozoos/inmunología , Células Th2/inmunología , Eficacia de las Vacunas , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/inmunologíaRESUMEN
Schistosome infection is regarded as one of the most important and neglected tropical diseases associated with poor sanitation. Like other living organisms, schistosomes employ multiple biological processes, of which some are regulated by a post-translational modification called Adenosine Diphosphate-ribosylation (ADP-ribosylation), catalyzed by ADP-ribosyltransferases. ADP-ribosylation is the addition of ADP-ribose moieties from Nicotinamide Adenine Dinucleotide (NAD+) to various targets, which include proteins and nucleotides. It is crucial in biological processes such as DNA repair, apoptosis, carbohydrate metabolism and catabolism. In the absence of a vaccine against schistosomiasis, this becomes a promising pathway in the identification of drug targets against various forms of this infection. The tegument of the worm is an encouraging immunogenic target for anti-schistosomal vaccine development. Vaccinology, molecular modeling and target-based drug discovery strategies have been used for years in drug discovery and for vaccine development. In this paper, we outline ADP-ribosylation and other different approaches to drug discovery and vaccine development against schistosomiasis.
Asunto(s)
ADP-Ribosilación/inmunología , Antihelmínticos/farmacología , Enfermedades Desatendidas/terapia , Schistosoma/inmunología , Esquistosomiasis/terapia , ADP-Ribosilación/efectos de los fármacos , Animales , Antihelmínticos/uso terapéutico , Antígenos Helmínticos/inmunología , Descubrimiento de Drogas/métodos , Humanos , Enfermedades Desatendidas/inmunología , Enfermedades Desatendidas/parasitología , Schistosoma/efectos de los fármacos , Esquistosomiasis/inmunología , Esquistosomiasis/parasitología , Desarrollo de Vacunas/métodosRESUMEN
BACKGROUND: Strongyloidiasis caused by Strongyloides stercoralis is a soil-transmitted helminthiasis affecting an estimated 370 million people and considered one of the most neglected tropical diseases. Although mostly distributed in tropical and subtropical areas, autochthonous infections have also been documented in north-eastern Italy, even though the transmission presumably stopped decades ago. Because of its peculiar auto-infective cycle, strongyloidiasis can persist lifelong, but the pathophysiological mechanisms associated with the maintenance of such a chronic infection are yet to be fully deciphered. METHODS: Serum levels of 23 immune factors were retrospectively assessed in a subgroup of participants in a randomised clinical trial for the treatment of strongyloidiasis (Strong Treat). Here we included Italian subjects born between 1931 and 1964 and diagnosed with strongyloidiasis between 2013 and 2017 (Ss+, n = 32). Serum samples obtained before (BT) and 6 months (6M AT) after ivermectin treatment, as well as from age- and gender-matched uninfected controls (CTRL, n = 34) were analysed. RESULTS: The assessed immune factors showed a general reduced concertation in Ss+ patients and a lack of association with eosinophilia. In our cohort, we did not observe the classical shift towards a type 2 immune response, since Th1 and Th2 cytokines were mostly unaltered. Instead, we observed chemokines as particularly affected by the presence of the parasite, since IL-8, CCL3, CCL4 and CCL5 were significantly reduced in concentration in Ss+ subjects compared to CTRL, suggesting that immune cell recruitment to the infection site might be dampened in these patients. This observation was further sustained by a significant increase of CCL4, CCL5 and CCL11 concentrations 6M AT. A significant raised systemic concentration of three growth factors, bFGF, PDGF-BB and IL-7 (haematopoietic growth factor) was also observed post-treatment, indicating a potential involvement in restoring tissue integrity and homeostasis following parasite elimination. CONCLUSIONS: These preliminary data suggest that, in order to survive for such a long period, S. stercoralis might suppress host responses that could otherwise result in its ejection. Our results offer novel insights in the potential mechanisms of disease tolerance that might take place during this chronic infection, including a potential T-cell hypo-responsiveness and a role for chemokines.
Asunto(s)
Factores Inmunológicos/sangre , Strongyloides stercoralis/inmunología , Estrongiloidiasis/inmunología , Anciano , Animales , Quimiocinas/sangre , Quimiocinas/inmunología , Enfermedad Crónica/tratamiento farmacológico , Citocinas/sangre , Citocinas/inmunología , Humanos , Inmunidad/fisiología , Terapia de Inmunosupresión , Péptidos y Proteínas de Señalización Intercelular/sangre , Péptidos y Proteínas de Señalización Intercelular/inmunología , Italia , Ivermectina/uso terapéutico , Enfermedades Desatendidas/inmunología , Estudios Retrospectivos , Estrongiloidiasis/tratamiento farmacológico , Linfocitos T/metabolismoRESUMEN
Studying emerging or neglected pathogens is often challenging due to insufficient information and absence of genetic tools. Dual RNA-seq provides insights into host-pathogen interactions, and is particularly informative for intracellular organisms. Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), an obligate intracellular bacterium that causes the vector-borne human disease scrub typhus. Half the Ot genome is composed of repetitive DNA, and there is minimal collinearity in gene order between strains. Integrating RNA-seq, comparative genomics, proteomics, and machine learning to study the transcriptional architecture of Ot, we find evidence for wide-spread post-transcriptional antisense regulation. Comparing the host response to two clinical isolates, we identify distinct immune response networks for each strain, leading to predictions of relative virulence that are validated in a mouse infection model. Thus, dual RNA-seq can provide insight into the biology and host-pathogen interactions of a poorly characterized and genetically intractable organism such as Ot.
Asunto(s)
Regulación Bacteriana de la Expresión Génica/inmunología , Interacciones Huésped-Patógeno/inmunología , Enfermedades Desatendidas/inmunología , Orientia tsutsugamushi/genética , Tifus por Ácaros/inmunología , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Estudios de Factibilidad , Femenino , Genoma Bacteriano , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interferón Tipo I/inmunología , Interferón Tipo I/metabolismo , Secuencias Repetitivas Esparcidas/genética , Ratones , Enfermedades Desatendidas/microbiología , Orientia tsutsugamushi/inmunología , Orientia tsutsugamushi/patogenicidad , Proteómica , ARN Bacteriano/genética , ARN Bacteriano/aislamiento & purificación , ARN Bacteriano/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , RNA-Seq , Tifus por Ácaros/microbiología , Transcripción Genética , Secuenciación del ExomaRESUMEN
Murine typhus is a neglected but widespread infectious disease that results in acute fever. The immunofluorescence assay (IFA) is the "gold standard" to identify IgM or IgG antibodies, although there is a lack of standardization in methodologies. The objective of this review is to summarize 1) the differences in published methodologies, 2) the diagnostic cutoff titers, and 3) the justification of diagnostic cutoffs. Searches were performed by combining the following search terms: "murine typhus," "rickettsia typhi," "immunofluorescence," "IFA," and "serologic" with restrictions (i.e., "rickettsia typhi" or "murine typhus," and "IFA" or "immunofluorescence," or "serologic*"). The search identified 78 studies that used IFA or immunoperoxidase assay (IIP) antibody cutoffs to diagnose murine typhus, 39 of which were case series. Overall, 45 studies (57.7%) provided little to no rationale as to how the cutoff was derived. Variation was seen locally in the cutoff titers used, but a 4-fold or greater increase was often applied. The cutoffs varied depending on the antibody target. No consensus was observed in establishing a cutoff, or for a single-value diagnostic cutoff. In conclusion, there is a lack of consensus in the establishment of a single-value cutoff. Further studies will need to be executed at each distinct geographic location to identify region-specific cutoffs, while also considering background antibody levels to distinguish between healthy and infected patients.
Asunto(s)
Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Enfermedades Desatendidas/diagnóstico , Rickettsia typhi/aislamiento & purificación , Tifus Endémico Transmitido por Pulgas/diagnóstico , Anticuerpos Antibacterianos/sangre , Técnica del Anticuerpo Fluorescente/estadística & datos numéricos , Humanos , Enfermedades Desatendidas/sangre , Enfermedades Desatendidas/inmunología , Enfermedades Desatendidas/microbiología , Valor Predictivo de las Pruebas , Rickettsia typhi/inmunología , Tifus Endémico Transmitido por Pulgas/sangre , Tifus Endémico Transmitido por Pulgas/inmunología , Tifus Endémico Transmitido por Pulgas/microbiologíaRESUMEN
BACKGROUND: The increased activity of regulatory B cells (Breg) is known to be involved in immunosuppression during helminth infection, which is characterized by inducing IL-10-producing Breg cells. However, the current knowledge of B cell subsets differentiation and IL-10-independent immunoregulatory mechanisms of B cells in schistosomiasis is insufficient. METHODS: BALB/c mice were percutaneously infected with cercariae for investigating the profile of B cell subsets during Schistosoma japonicum infection. B cells isolated from the spleen or peritoneal cavity were analyzed for the regulatory phenotype after stimulation with soluble egg antigens (SEA) in vitro. CD4+ T cells were then cocultured with B cells pretreated with or without anti-PD-L1 antibody for investigating the role of B cells from infected mice on regulating CD4+ T cells. Furthermore, the in vivo administration of anti-PD-L1 antibody was conducted to investigate the role of PD-L1 in regulating host immunity during infection. RESULTS: The percentages of peritoneal and splenic B-1a cells, as well as marginal zone B (MZB) cells were decreased at eight and twelve weeks after infection compared to those from uninfected mice. In splenic B cells, TGF-ß expression was increased at eight weeks but declined at twelve weeks of infection, and PD-L1 expression was elevated at both eight and twelve weeks of infection. In addition, SEA stimulation in vitro significantly promoted the expression of IL-10 in peritoneal B cells and CD5 in splenic B cells, and the SEA-stimulated splenic and peritoneal B cells preferentially expressed PD-L1 and TGF-ß. The splenic B cells from infected mice were able to suppress the function of Th1 and Th2 cells in vitro but to expand the expression of Tfh transcription factor Bcl6, which was further enhanced by blocking PD-L1 of B cells before co-cultivation. Moreover, Th2 response and Bcl6 expression in CD4+ T cells were also increased in vivo by blocking PD-L1 after infection, although the hepatic pathology was slightly influenced. CONCLUSIONS: Our findings revealed that S. japonicum infection modulates the differentiation of B cell subsets that have the capability to affect the CD4+ T cell response. This study contributes to a better understanding of B cells immune response during schistosomiasis.
Asunto(s)
Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Enfermedades Desatendidas/inmunología , Fenotipo , Esquistosomiasis Japónica/inmunología , Animales , Subgrupos de Linfocitos B/inmunología , Antígeno B7-H1/inmunología , Diferenciación Celular , Modelos Animales de Enfermedad , Femenino , Interleucina-10/inmunología , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Bazo/inmunología , Células TH1 , Células Th2/inmunología , Factor de Crecimiento Transformador betaRESUMEN
BACKGROUND: Different immune mechanisms are capable of killing developmental stages of filarial nematodes and these mechanisms are also likely to vary between the primary and a challenge infection. However, the lack of a detailed analysis of cytokine, chemokine and immunoglobulin levels in human loiasis is still evident. Therefore, detailed analysis of immune responses induced by the different developmental stages of Loa loa in immune-competent BALB/c mice will aid in the characterization of distinct immune responses that are important for the immunity against loiasis. METHODS: Different developmental stages of L. loa were obtained from human peripheral blood (microfilariae, MF), the transmitting vector, Chrysops (larval stage 3, L3) and infected immune-deficient BALB/cRAG2γc-/- mice (L4, L5, adult worms). Groups of wildtype BALB/c mice were then injected with the isolated stages and after 42 days post-infection (pi), systemic cytokine, chemokine and immunoglobulin levels were determined. These were then compared to L. loa-specific responses from in vitro re-stimulated splenocytes from individual mice. All parameters were determined using Luminex technology. RESULTS: In a pilot study, BALB/c mice cleared the different life stages of L. loa within 42 days pi and systemic cytokine, chemokine and immunoglobulin levels were equal between infected and naive mice. Nevertheless, L. loa-specific re-stimulation of splenocytes from mice infected with L5, MF or adult worms led to induction of Th2, Th17 and chemokine secretion patterns. CONCLUSIONS: This study shows that although host immunity remains comparable to naive mice, clearance of L. loa life-cycle development stages can induce immune cell memory leading to cytokine, chemokine and immunoglobulins secretion patterns which might contribute to immunity and protection against reinfection.
Asunto(s)
Inmunidad Humoral , Estadios del Ciclo de Vida/inmunología , Loa/inmunología , Loiasis/inmunología , Ratones Endogámicos BALB C/inmunología , Animales , Antígenos Helmínticos/sangre , Citocinas/sangre , Dípteros/parasitología , Humanos , Inmunoglobulinas/sangre , Insectos Vectores/parasitología , Larva/parasitología , Ratones , Ratones Endogámicos BALB C/parasitología , Enfermedades Desatendidas/inmunología , Células Th17/inmunología , Células Th2/inmunologíaRESUMEN
Human lymphatic filariasis (LF), a parasitic infection caused by the nematodes Wuchereria bancrofti, Brugia malayi and B. timori, and transmitted by mosquito, results in a debilitating disease commonly identified as 'elephantiasis'. LF affects millions of people in India and several other tropical and sub-tropical countries imposing a huge economic burden on governments due to disability associated loss of man-hours and for disease management. Efforts to control the infection by WHO's mass drug administration (MDA) strategy using three antifilarials diethylcarbamazine, albendazole and ivermectin are only partly successful and therefore, there is an immediate need for alternative strategies. Some of the alternative strategies being explored in laboratories are: enhancing the immune competence of host by immunomodulation, combining immunomodulation with antifilarials, identifying immunoprophylactic parasite molecules (vaccine candidates) and identifying parasite molecules that can be potential drug targets. This review focuses on the advances made in this direction.
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Filariasis Linfática/tratamiento farmacológico , Filaricidas/farmacología , Sistema Inmunológico/efectos de los fármacos , Enfermedades Desatendidas/tratamiento farmacológico , Filariasis Linfática/inmunología , Humanos , Sistema Inmunológico/inmunología , Enfermedades Desatendidas/inmunología , Pruebas de Sensibilidad ParasitariaRESUMEN
Neglected tropical diseases (NTDs) share certain traits: they are parasitic infections, prevailing in tropical environments and affecting marginalized sectors of the population. Six NTDs - ascariasis, cysticercosis, echinococcosis, hookworm infection, onchocerciasis and trichuriasis - all of them endemic in Latin America and the Caribbean (LAC), are analysed in this work. This review aims to discuss key information on the function of excretory/secretory (E/S) proteins from these parasites in their infectivity, pathogeny and diagnosis. The modulation of the host immune system to favour the permanence and survival of the parasite is also discussed. An updated knowledge on the function of E/S molecules in endemic parasitoses in LAC may lead to new approaches for the clinical management and diagnosis of these diseases. In turn, this could allow us to optimize their treatment and make it more affordable - a relevant goal given the economic constraints that the region is facing.
Asunto(s)
Enfermedades Endémicas , Proteínas del Helminto/fisiología , Helmintiasis/epidemiología , Sistema Inmunológico/parasitología , Enfermedades Desatendidas/parasitología , Animales , Región del Caribe/epidemiología , Manejo de la Enfermedad , Helmintiasis/inmunología , Helmintiasis/parasitología , Interacciones Huésped-Parásitos , Humanos , América Latina/epidemiología , Enfermedades Desatendidas/epidemiología , Enfermedades Desatendidas/inmunología , Medicina TropicalRESUMEN
BACKGROUND: Mali has become increasingly interested in the evaluation of transmission of both Wuchereria bancrofti and Onchocerca volvulus as prevalences of both infections move toward their respective elimination targets. The SD Bioline Onchocerciasis/LF IgG4 Rapid Test was used in 2 evaluation units (EU) to assess its performance as an integrated surveillance tool for elimination of lymphatic filariasis (LF) and onchocerciasis. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional survey with SD Bioline Onchocerciasis/LF IgG4 Rapid Test was piggy-backed onto a transmission assessment survey (TAS) (using the immunochromatographic card test (ICT) Binax Filariasis Now test for filarial adult circulating antigen (CFA) detection) for LF in Mali among 6-7 year old children in 2016 as part of the TAS in two EUs namely Kadiolo-Kolondieba in the region of Sikasso and Bafoulabe -Kita-Oussoubidiagna-Yelimane in the region of Kayes. In the EU of Kadiolo- Kolondieba, of the 1,625 children tested, the overall prevalence of W. bancrofti CFA was 0.62% (10/1,625) [CI = 0.31-1.09]; while that of IgG4 to Wb123 was 0.19% (3/1,600) [CI = 0.04-0.50]. The number of positives tested with the two tests were statistically comparable (p = 0.09). In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of W. bancrofti CFA was 0% (0/1,700) and that of Wb123 IgG4 antibody was 0.06% (1/1,700), with no statistically significant difference between the two rates (p = 0.99). In the EU of Kadiolo- Kolondieba, the prevalence of Ov16-specific IgG4 was 0.19% (3/1,600) [CI = 0.04-0.50]. All 3 positives were in the previously O. volvulus-hyperendemic district of Kolondieba. In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of Ov16-specific IgG4 was 0.18% (3/1,700) [CI = 0.04-0.47]. These 3 Ov16 IgG4 positives were from previously O.volvulus-mesoendemic district of Kita. CONCLUSIONS/SIGNIFICANCE: The SD Bioline Onchocerciasis/LF IgG4 Rapid test appears to be a good tool for integrated exposure measures of LF and onchocerciasis in co-endemic areas.
Asunto(s)
Anticuerpos Antihelmínticos/inmunología , Filariasis Linfática/inmunología , Inmunoglobulina G/inmunología , Onchocerca volvulus/inmunología , Oncocercosis/inmunología , Wuchereria bancrofti/inmunología , Animales , Anticuerpos Antihelmínticos/sangre , Niño , Estudios Transversales , Filariasis Linfática/sangre , Filariasis Linfática/epidemiología , Filariasis Linfática/parasitología , Humanos , Inmunoglobulina G/sangre , Pruebas Inmunológicas , Malí/epidemiología , Enfermedades Desatendidas/sangre , Enfermedades Desatendidas/epidemiología , Enfermedades Desatendidas/inmunología , Enfermedades Desatendidas/parasitología , Oncocercosis/sangre , Oncocercosis/epidemiología , Oncocercosis/parasitología , Estudios SeroepidemiológicosAsunto(s)
Vacunas Bacterianas/inmunología , Enfermedades Transmisibles Emergentes/terapia , Inmunoterapia/métodos , Lepra/terapia , Enfermedades Desatendidas/terapia , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Adulto , Animales , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/uso terapéutico , Niño , Enfermedades Transmisibles Emergentes/tratamiento farmacológico , Enfermedades Transmisibles Emergentes/inmunología , Enfermedades Transmisibles Emergentes/prevención & control , Modelos Animales de Enfermedad , Humanos , Leprostáticos/administración & dosificación , Leprostáticos/uso terapéutico , Lepra/tratamiento farmacológico , Lepra/inmunología , Lepra/prevención & control , Mycobacterium leprae/efectos de los fármacos , Mycobacterium leprae/inmunología , Enfermedades Desatendidas/tratamiento farmacológico , Enfermedades Desatendidas/inmunología , Enfermedades Desatendidas/prevención & control , Profilaxis Posexposición , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/uso terapéuticoRESUMEN
Melioidosis is a major neglected tropical disease with high mortality, caused by the Gram-negative bacterium Burkholderia pseudomallei (Bp). Microbiological culture remains the gold standard for diagnosis, but a simpler and more readily available test such as an antibody assay is highly desirable. In this study, we conducted a serological survey of blood donors (n = 1,060) and adult melioidosis patients (n = 200) in northeast Thailand to measure the antibody response to Bp using the indirect hemagglutination assay (IHA). We found that 38% of healthy adults (aged 17-59 years) have seropositivity (IHA titer ≥ 1:80). The seropositivity in healthy blood donors was associated with having a declared occupation of rice farmer and with residence in a nonurban area, but not with gender or age. In the melioidosis cohort, the seropositivity rate was higher in adult patients aged between 18 and 45 years (90%, 37/41) compared with those aged ≥ 45 years (68%, 108/159, P = 0.004). The seropositivity rate was significantly higher in people with diabetes (P = 0.008). Seropositivity was associated with decreased mortality on univariable analysis (P = 0.005), but not on multivariable analysis when adjusted for age, diabetes status, preexisting renal disease, and neutrophil count. This study confirms the presence of high background antibodies in an endemic region and demonstrates the limitations of using IHA during acute melioidosis in this population.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Burkholderia pseudomallei/inmunología , Complicaciones de la Diabetes/inmunología , Pruebas de Hemaglutinación/métodos , Melioidosis/inmunología , Enfermedades Desatendidas/inmunología , Adolescente , Adulto , Agricultura , Burkholderia pseudomallei/aislamiento & purificación , Burkholderia pseudomallei/patogenicidad , Estudios de Cohortes , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/mortalidad , Femenino , Humanos , Masculino , Melioidosis/diagnóstico , Melioidosis/microbiología , Melioidosis/mortalidad , Persona de Mediana Edad , Enfermedades Desatendidas/diagnóstico , Enfermedades Desatendidas/microbiología , Enfermedades Desatendidas/mortalidad , Neutrófilos/inmunología , Neutrófilos/patología , Población Rural , Análisis de Supervivencia , Tailandia/epidemiologíaRESUMEN
Purinergic receptors are widespread in the human organism and are involved in several physiological functions like neurotransmission, nociception, platelet aggregation, etc. In the immune system, they may regulate the expression and release of pro-inflammatory factors as well as the activation and death of several cell types. It is already described the participation of some purinergic receptors in the inflammation and pathological processes, such as a few neglected tropical diseases (NTDs) which affect more than 1 billion people in the world. Although the high social influence those diseases represent endemic countries, most of them do not have an efficient, safe or affordable drug treatment. In that way, this review aims to discuss the current literature involving purinergic receptor and immune response to NTDs pathogens, which may contribute in the search for new therapeutic possibilities.
Asunto(s)
Enfermedades Desatendidas/tratamiento farmacológico , Receptores Purinérgicos/metabolismo , Medicina Tropical/métodos , Animales , Humanos , Inmunidad , Inflamación , Terapia Molecular Dirigida/métodos , Enfermedades Desatendidas/inmunología , Enfermedades Desatendidas/patología , Transducción de Señal/efectos de los fármacosRESUMEN
Hookworm is a major public health concern, yet still relatively little is known about the immunological responses involved in human infection. Animal studies are mainly confined to using the natural rodent helminth Nippostrongylus brasiliensis as this has been proposed as the most accurate model of hookworm infection in the mouse, with both its life cycle and the immune responses it invokes having been extremely well characterized. In this review, we examine the roles that type 2 innate lymphoid cells (ILC2s) play in immunity and host tolerance to hookworm infection, particularly N. brasiliensis. This includes their role in the initiation and regulation of immune responses, as well as in the resolution and limitation of tissue damage required after an infection with a large organism, such as a helminth.