RESUMO
Infection with helminth parasites evokes a complex cellular response in the host, where granulocytes (i.e. eosinophils, basophils and mast cells (MCs)) feature prominently. In addition to being used as markers of helminthic infections, MCs have been implicated in worm expulsion since animals defective in c-kit signaling, which results in diminished MC numbers, can have delayed worm expulsion. The role of MCs in the rejection of the rat tapeworm, Hymenolepsis diminuta, from the non-permissive mouse host is not known. MC-deficient mice display a delay in the expulsion of H. diminuta that is accompanied by a less intense splenic Th2 response, as determined by in vitro release of interleukin (IL)-4, IL-5 and IL-13 cytokines. Moreover, worms retrieved from MC-deficient mice were larger than those from wild-type (WT) mice. Assessment of gut-derived IL-25, IL-33, thymic stromal lymphopoietin revealed lower levels in uninfected MC-deficient mice compared with WT, suggesting a role for MCs in homeostatic control of these cytokines: differences in these gut cytokines between the mouse strains were not observed after infection with H. diminuta Finally, mice infected with H. diminuta display less severe dinitrobenzene sulphonic acid (DNBS)-induced colitis, and this beneficial effect of the worm was unaltered in MC-deficient mice challenged with DNBS, as assessed by a macroscopic disease score. Thus, while MCs are not essential for rejection of H. diminuta from mice, their absence slows the kinetics of expulsion allowing the development of greater worm biomass prior to successful rejection of the parasitic burden.
Assuntos
Infecções por Cestoides/imunologia , Colite/imunologia , Interações Hospedeiro-Parasita/imunologia , Mastócitos/imunologia , Animais , Biomassa , Infecções por Cestoides/parasitologia , Colite/induzido quimicamente , Colite/parasitologia , Dinitrofluorbenzeno/análogos & derivados , Dinitrofluorbenzeno/toxicidade , Humanos , Hymenolepis diminuta/imunologia , Hymenolepis diminuta/patogenicidade , Mastócitos/parasitologia , Camundongos , Ratos , Baço/parasitologia , Células Th2/imunologia , Células Th2/parasitologiaRESUMO
Parasite infection impacts population dynamics through effects on fitness and fecundity of the individual host. In addition to the known roles of environmental factors, host susceptibility to parasites has a genetic basis that has not been well characterized. We previously mapped quantitative trait loci (QTL) for susceptibility to rat tapeworm (Hymenolepis diminuta) infection in Tribolium castaneum using dominant AFLP markers; however, the resistance genes were not identified. Here, we refined the QTL locations and increased the marker density in the QTL regions using new microsatellite markers, sequence-tagged site markers, and single-strand conformational polymorphism markers. Resistance QTL in three linkage groups (LG3, LG6, and LG8) were each mapped to intervals <1.0 cM between two codominant markers. The effects of 21 genes in the three QTL regions were investigated by using quantitative RT-PCR analysis, and transcription profiles were obtained from the resistant TIW1 and the susceptible cSM strains. Based on transcription data, eight genes were selected for RNA interference analysis to investigate their possible roles in H. diminuta resistance, including cytochrome P450 (LOC657454) and Toll-like receptor 13 (TLR13, LOC662131). The transcription of P450 and TLR13 genes in the resistant TIW1 strains was reduced more than ninefold relative to the control. Moreover, the effects of gene knockdown of P450 and TLR13 caused resistant beetles to become susceptible to tapeworm infection, which strongly suggests an important role for each in T. castaneum resistance to H. diminuta infection.
Assuntos
Resistência à Doença/genética , Genes de Insetos , Himenolepíase/imunologia , Tribolium/genética , Animais , Mapeamento Cromossômico , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Himenolepíase/genética , Hymenolepis diminuta/patogenicidade , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Repetições de Microssatélites , Polimorfismo Conformacional de Fita Simples , Locos de Características Quantitativas , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Transcrição Gênica , Tribolium/parasitologiaRESUMO
We report a case of Hymenolepis diminuta infection in a 2-year-old Malaysian child. This case was initially reported as 'normal' after the examination of proglottids shed from the anus of the child at a private laboratory on two occasions. The putative proglottids shed was then referred to the Parasite Southeast Asia Diagnostic (Para:SEAD) Laboratory, Department of Parasitology, Faculty of Medicine, University of Malaya for further examination. Microscopic examination confirmed that the child was infected with H. diminuta based on the characteristic eggs found in the proglottids. She was treated with a single dose praziquantel (20 mg/kg of body weight) and recovered well.
Assuntos
Himenolepíase/diagnóstico , Hymenolepis diminuta/isolamento & purificação , Praziquantel/uso terapêutico , Animais , Pré-Escolar , Ovos , Fezes/parasitologia , Feminino , Humanos , Himenolepíase/tratamento farmacológico , Himenolepíase/parasitologia , Hymenolepis diminuta/patogenicidadeRESUMO
While parasites and immunity are widely believed to play important roles in the evolution of male ornaments, their potential influence on systems where male weaponry is the object of sexual selection is poorly understood. We experimentally infect larval broad-horned flour beetles with a tapeworm and study the consequent effects on: 1) adult male morphology 2) male-male contests for mating opportunities, and 3) induction of the innate immune system. We find that infection significantly reduces adult male size in ways that are expected to reduce mating opportunities in nature. The sum of our morphological, competition, and immunological data indicate that during a life history stage where no new resources are acquired, males allocate their finite resources in a way that increases future mating potential.
Assuntos
Evolução Biológica , Besouros/fisiologia , Besouros/parasitologia , Comportamento Competitivo , Preferência de Acasalamento Animal , Comportamento Sexual Animal , Animais , Copulação , Cornos , Himenolepíase/imunologia , Himenolepíase/parasitologia , Hymenolepis diminuta/patogenicidade , Imunidade Celular , Masculino , ReproduçãoRESUMO
Explanations for the evolution of pathogen-induced fecundity reduction usually rely on a common principle: the trade-off between host longevity and reproduction. Recent advances in nutritional research have, however, challenged this assumption and shown that longevity and reproduction are not inextricably linked. In this study, we showed that beetles infected by cysticercoids of the tapeworm Hymenolepis diminuta increased their total food intake and, more particularly, their carbohydrate consumption compared with uninfected insects. This increased intake was only pronounced during the first 12 days p.i., when the parasite grows and develops into a mature metacestode. Despite consuming more nutrients, infected individuals sustained lower levels of body lipid and were less efficient at converting ingested protein to body protein. However they demonstrated a capacity to compose a diet that sustained high levels of reproductive output unless confined to foods that were nutritionally dilute. We did not find any indication that macronutrient intakes had an effect on host pro-phenoloxidase activity; however, phenoloxidase activity was significantly affected by protein intake. Our results showed that when offered nutritionally complementary diets, infected hosts do not systematically suffer a reduction in fecundity. Thus, in our view, the assumption that a reduction in host reproduction represents an adaptive response by the host or the parasite to divert resources away from reproduction toward other traits should be reassessed.
Assuntos
Besouros/fisiologia , Besouros/parasitologia , Hymenolepis diminuta/patogenicidade , Animais , Catecol Oxidase/metabolismo , Besouros/química , Precursores Enzimáticos/metabolismo , Comportamento Alimentar , Fertilidade , Lipídeos/análise , Monofenol Mono-Oxigenase/metabolismo , Proteínas/análiseRESUMO
The non-invasive parasitic cestode Hymenolepis diminuta induces hypertrophy, hyperplasia and other changes in cell activity in the intestine of rats which are indicated in the expression of mRNA. We have investigated various house-keeping genes (GAPDH, beta-actin, 18S and HPRT) and other internal controls (total RNA/unit biomass, total RNA/unit length of intestine) to validate gene expression in the rat intestine after cestode infection and drug-induced neuromodulation. Variation in GAPDH, beta-actin, 18S and HPRT expression was observed in rat jejunal tissue according to treatment. Total RNA/unit length of intestine was found to be the most suitable internal control for normalizing target gene mRNA expression in both infected and/or drug-induced rat intestine. This normalization method may be applied to studies of gene expression levels in intestinal tissue where hypertrophy, hyperplasia, rapid growth and cell differentiation generally occur.
Assuntos
Perfilação da Expressão Gênica/normas , Himenolepíase/parasitologia , Hymenolepis diminuta/patogenicidade , Mucosa Intestinal/metabolismo , RNA Mensageiro , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Animais , Regulação da Expressão Gênica , Himenolepíase/fisiopatologia , Intestinos/parasitologia , Masculino , Proteínas/genética , Proteínas/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Padrões de ReferênciaRESUMO
BACKGROUND & AIMS: There is convincing evidence from animal and human studies that infection with parasitic helminths can alleviate the histopathology and symptoms of colitis. Here the ability of the rat tapeworm Hymenolepis diminuta to affect the course of oxazolone-induced colitis (a TH2 model) was assessed. METHODS: Mice were infected with H diminuta and 8 days later they received oxazolone (3 mg in 50% EtOH, intrarectal). On autopsy (3 or 7 days postoxazolone), disease severity was assessed by macroscopic clinical scores, histologic damage scores, myeloperoxidase and eosinophil peroxidase activity, and cytokine synthesis. RESULTS: As gauged by all markers of gut function, infection with H diminuta caused a significant exacerbation of oxazolone-induced colitis. Indeed, while mice receiving oxazolone only began to recover approximately 3-4 days posttreatment, the cotreated group continued to deteriorate. Helminth infection, independent of oxazolone administration, enhanced IL-4, IL-5, IL-10, and IL-13 production from in vitro stimulated immune cells and evoked increases in colonic eosinophil peroxidase of cotreated mice. Finally, while knockout of natural killer (NK) and NK-T cells by administration of a neutralizing NK1.1 antibody reduced the inflammation in oxazolone and oxazolone + H diminuta-treated animals, mice in the latter group still displayed significant colitis. CONCLUSIONS: We have shown that H diminuta infection is beneficial in other models of colitis. The current data is presented as a caveat to the position that parasitic helminths in general can be considered as a therapy for heterogeneous inflammatory disorders without careful analysis of the immunologic basis of the condition.
Assuntos
Colite/patologia , Colo/patologia , Himenolepíase/complicações , Hymenolepis diminuta/patogenicidade , Adjuvantes Imunológicos/toxicidade , Animais , Antígenos Ly , Antígenos de Superfície/imunologia , Biomarcadores/metabolismo , Colite/induzido quimicamente , Colite/complicações , Colo/imunologia , Colo/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Peroxidase de Eosinófilo/metabolismo , Seguimentos , Himenolepíase/metabolismo , Himenolepíase/patologia , Interleucina-10/biossíntese , Interleucina-13/biossíntese , Interleucina-4/biossíntese , Interleucina-5/biossíntese , Células Matadoras Naturais/imunologia , Lectinas Tipo C/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Subfamília B de Receptores Semelhantes a Lectina de Células NK , Oxazolona/toxicidade , Peroxidase/metabolismo , Taxa de SobrevidaRESUMO
Information on the molecular basis of resistance and the evolution of resistance is crucial to an understanding of the appearance, spread, and distribution of resistance genes and of the mechanisms of host adaptation in natural populations. One potential important genetic constraint for the evolution of resistance is fitness cost associated with resistance. To determine whether host resistance to parasite infection is associated with fitness costs, we conducted simultaneous quantitative trait loci (QTL) mapping of resistance to parasite infection and fitness traits using the red flour beetle (Tribolium castaneum) and the tapeworm parasite (Hymenolepis diminuta) system in two independent segregating populations. A genome-wide QTL scan using amplified fragment length polymorphism (AFLP) markers revealed three QTL for beetle resistance to tapeworm infection. These three QTL account for 44-58% variance in beetle infection intensity. We identified five QTL for fecundity and five QTL for egg-to-adult viability, which accounted for 36-57% and 36-49%, respectively, of the phenotypic variance in fecundity and egg-to-adult viability. The three QTL conferring resistance were colocalized with the QTL affecting beetle fitness. The genome regions that contain the QTL for parasite resistance explained the majority of the variance in fecundity and egg-to-adult viability in the mapping populations. Colocalization of QTL conferring resistance to parasite infection and beetle fitness may result from the pleiotropic effects of the resistance genes on host fitness or from tight linkages between resistance genes and adverse deleterious mutations. Therefore, our results provide evidence that the genome regions conferring resistance to tapeworm infection are partially responsible for fitness costs in the resistant beetle populations.