RESUMO
Trypanosoma rangeli is a non-pathogenic protozoan parasite that infects mammals, including humans, in Chagas disease-endemic areas of South and Central America. The parasite is transmitted to a mammalian host when an infected triatomine injects metacyclic trypomastigotes into the host's skin during a bloodmeal. Infected mammals behave as parasite reservoirs for several months and despite intensive research, some major aspects of T. rangeli-vertebrate interactions are still poorly understood. In particular, many questions still remain unanswered, e.g. parasite survival and development inside vertebrates, as no parasite multiplication sites have yet been identified. The present study used an insect bite transmission strategy to investigate whether the vector inoculation spot in the skin behave as a parasite-replication site. Histological data from the skin identified extracellular parasites in the dermis and hypodermis of infected mice in the first 24 hours post-infection, as well as the presence of inflammatory infiltrates in a period of up to 7 days. However, qPCR analyses demonstrated that T. rangeli is eliminated from the skin after 7 days of infection despite being still consistently found on circulating blood and secondary lymphoid tissues for up to 30 days post-infection. Interestingly, significant numbers of parasites were found in the spleen and mesenteric lymph nodes of infected mice during different periods of infection and steady basal numbers of flagellates are maintained in the host's bloodstream, which might behave as a transmission source to insect vectors. The presence of parasites in the spleen was confirmed by fluorescent photomicrography of free and cell-associated T. rangeli forms. Altogether our results suggest that this organ could possibly behave as a T. rangeli maintenance hotspot in vertebrates.
Assuntos
Doença de Chagas/transmissão , Linfonodos/parasitologia , Pele/parasitologia , Baço/parasitologia , Trypanosoma rangeli/isolamento & purificação , Animais , América Central/epidemiologia , Doença de Chagas/epidemiologia , Modelos Animais de Doenças , Interações Hospedeiro-Parasita , Humanos , Mordeduras e Picadas de Insetos/parasitologia , Insetos Vetores/parasitologia , Camundongos , Rhodnius/parasitologia , Sepse/parasitologia , América do Sul/epidemiologiaRESUMO
INTRODUCTION: Biliary ascariasis, although uncommon, can lead to infectious complications and severe outcomes. This study reported three patients with biliary ascariasis and who were admitted to a paediatric hospital in Salvador, Brazil. CASE REPORTS: Case 1: A 1-year-old boy, with HIV, hospitalised with diarrhoea, fever, pain, and abdominal distension. He underwent an exploratory laparotomy, which showed peritonitis secondary to a perforation of the hepatic duct by ascaris. Case 2: A 3-year-old boy admitted with fever, abdominal pain and jaundice. Imaging examination was suggestive of ascaris in the intrahepatic biliary tract and a hepatic abscess. Case 3: A 7-year-old boy who was hospitalised with a history of abdominal colic, jaundice and fever, with a suggestive image of ascaris in the biliary tract and evolution to sepsis. DISCUSSION: Three cases of biliary ascariasis were reported with severe infectious complications involving peritonitis, hepatic abscess and sepsis. CONCLUSION: In endemic regions, biliary ascariasis should be considered in cases with jaundice, abdominal pain and fever, due to its morbidity and risk of complications.
Assuntos
Ascaríase/complicações , Ascaríase/diagnóstico , Infecções Bacterianas/parasitologia , Doenças Biliares/diagnóstico , Doenças Biliares/parasitologia , Coinfecção , Animais , Ascaríase/diagnóstico por imagem , Doenças Biliares/complicações , Doenças Biliares/diagnóstico por imagem , Brasil , Criança , Pré-Escolar , Hospitais Pediátricos , Humanos , Lactente , Abscesso Hepático/parasitologia , Masculino , Peritonite/parasitologia , Sepse/parasitologiaRESUMO
BACKGROUND: Macrophage migration inhibitory factor (MIF) is essential for controlling parasite burden and survival in a model of systemic Toxoplasma gondii infection. Peroral T. gondii infection induces small intestine necrosis and death in susceptible hosts, and in many aspects resembles inflammatory bowel disease (IBD). Considering the critical role of MIF in the pathogenesis of IBD, we hypothesized that MIF participates in the inflammatory response induced by oral infection with T. gondii. METHODOLOGY/PRINCIPAL FINDINGS: Mif deficient (Mif(-/-)) and wild-type mice in the C57Bl/6 background were orally infected with T. gondii strain ME49. Mif(-/-) mice had reduced lethality, ileal inflammation and tissue damage despite of an increased intestinal parasite load compared to wt mice. Lack of MIF caused a reduction of TNF-α, IL-12, IFN-γ and IL-23 and an increased expression of IL-22 in ileal mucosa. Moreover, suppressed pro-inflammatory responses at the ileal mucosa observed in Mif(-/-) mice was not due to upregulation of IL-4, IL-10 or TGF-ß. MIF also affected the expression of matrix metalloproteinase-9 (MMP-9) but not MMP-2 in the intestine of infected mice. Signs of systemic inflammation including the increased concentrations of inflammatory cytokines in the plasma and liver damage were less pronounced in Mif(-/-) mice compared to wild-type mice. CONCLUSION/SIGNIFICANCE: In conclusion, our data suggested that in susceptible hosts MIF controls T. gondii infection with the cost of increasing local and systemic inflammation, tissue damage and death.
Assuntos
Fatores Inibidores da Migração de Macrófagos/metabolismo , Boca/parasitologia , Toxoplasma/fisiologia , Toxoplasmose/patologia , Toxoplasmose/parasitologia , Animais , Citocinas/metabolismo , Ileíte/complicações , Ileíte/parasitologia , Ileíte/patologia , Íleo/parasitologia , Íleo/patologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/enzimologia , Mucosa Intestinal/parasitologia , Mucosa Intestinal/patologia , Fatores Inibidores da Migração de Macrófagos/deficiência , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Carga Parasitária , Sepse/complicações , Sepse/parasitologia , Sepse/patologia , Análise de Sobrevida , Toxoplasmose/complicaçõesRESUMO
Malaria-induced sepsis is associated with an intense proinflammatory cytokinemia for which the underlying mechanisms are poorly understood. It has been demonstrated that experimental infection of humans with Plasmodium falciparum primes Toll-like receptor (TLR)-mediated proinflammatory responses. Nevertheless, the relevance of this phenomenon during natural infection and, more importantly, the mechanisms by which malaria mediates TLR hyperresponsiveness are unclear. Here we show that TLR responses are boosted in febrile patients during natural infection with P. falciparum. Microarray analyses demonstrated that an extraordinary percentage of the up-regulated genes, including genes involving TLR signaling, had sites for IFN-inducible transcription factors. To further define the mechanism involved in malaria-mediated "priming," we infected mice with Plasmodium chabaudi. The human data were remarkably predictive of what we observed in the rodent malaria model. Malaria-induced priming of TLR responses correlated with increased expression of TLR mRNA in a TLR9-, MyD88-, and IFNgamma-dependent manner. Acutely infected WT mice were highly susceptible to LPS-induced lethality while TLR9(-/-), IL12(-/-) and to a greater extent, IFNgamma(-/-) mice were protected. Our data provide unprecedented evidence that TLR9 and MyD88 are essential to initiate IL12 and IFNgamma responses and favor host hyperresponsiveness to TLR agonists resulting in overproduction of proinflammatory cytokines and the sepsis-like symptoms of acute malaria.