NFAT1 Regulates Ly6Chi Monocyte Recruitment to the CNS and Plays an Essential Role in Resistance to Toxoplasma gondii Infection.

Monocytes play key roles in the maintenance of homeostasis and in the control of the infection. Monocytes are recruited from the bone marrow to inflammatory sites and are essential for antimicrobial activity to limit tissue damage and promote adaptive T cell responses. Here, we investigated the role of Nuclear Factor of Activated T cells 1 (NFAT1) in the regulation of Ly6Chi inflammatory monocyte recruitment to the CNS upon T. gondii infection. We show that NFAT-1-deficient monocytes are unable to migrate to the CNS of T. gondii-infected mice. Moreover, NFAT1-/- mice are highly susceptible to chronic T. gondii infection due to a failure to control parasite replication in the CNS. The inhibition of Ly6Chi inflammatory monocyte recruitment to the CNS severely blocked CXCL10 production and consequently the migration of IFN-γ-producing CD4+ T cells. Moreover, the transfer of Ly6Chi monocytes to infected NFAT1-/- mice favored CD4+ T cell migration to the CNS and resulted in the inhibition of parasite replication and host defense. Together, these results demonstrated for the first time the contribution of NFAT1 to the regulation of Ly6Chi monocyte recruitment to the CNS and to resistance during chronic T. gondii infection.

Immunodiagnosis of CNS parasitic infections.

The nature of many parasitic infections of the central nervous system (CNS) requires immunodiagnosis to confirm presumptive diagnoses. The CNS is the primary site of parasite infection for some parasitic organisms and for others, neurological infection occurs only in immunocompromised hosts. Still other parasites cause ectopic infections of the CNS and occur very rarely. This review concentrates on laboratory diagnosis of diseases that are caused by parasites with a primary predilection for the CNS. Emphasis is placed on laboratory diagnostic methods that are used and suitable for clinical diagnosis, rather than a comprehensive review of all the experimental methods that have been reported in the literature. Immunodiagnosis is not appropriate for the diagnosis of all parasitic infections of the CNS; in those cases, alternative diagnostic methods are presented, but not discussed in detail. In some instances potential new antigens or methods are presented, particularly if adoption of these methods is expected in the near future.

Mechanisms of CNS invasion and damage by parasites.

Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection.

[The immunologic factors in cerebrospinal liquor under bacterial, fungous or parasitic neuro-infections: a literature review].

The prognosis of course and outcome of inflectional inflammatory diseases of central nervous system, indicators of inflammatory reaction and immune response in cerebrospinal liquor in patients has been investigated.

Trichobilharzia regenti: host immune response in the pathogenesis of neuroinfection in mice.

Besides their natural bird hosts, Trichobilharzia regenti cercariae are able to penetrate skin of mammals, including humans. Experimental infections of mice showed that schistosomula of this species are able to avoid the immune response in skin of their non-specific mammalian host and escape the skin to migrate to the CNS. Schistosomula do not mature in mammals, but can survive in nervous tissue for several days post infection. Neuroinfections of specific bird hosts as well as accidental mammalian hosts can lead to neuromotor effects, for example, leg paralysis and thus this parasite serves as a model of parasite invasion of the CNS. Here, we show by histological and immunohistochemical investigation of CNS invasion of immunocompetent (BALB/c) and immunodeficient (SCID) mice by T. regenti schistosomula that the presence of parasites in the nervous tissue initiated an influx of immune cells, activation of microglia, astrocytes and development of inflammatory lesions. Schistosomula elimination in the tissue depended on the host immune status. In the absence of CD3+ T-cells in immunodeficient SCID mice, parasite destruction was slower than that in immunocompetent BALB/c mice. Axon injury and subsequent secondary demyelination in the CNS were associated with mechanical damage due to migration of schistosomula through the nervous tissue, and not by host immune processes. Immunoreactivity of the parasite intestinal content for specific antigens of oligodendrocytes/myelin and neurofilaments showed for the first time that schistosomula ingest the nervous tissue components during their migration.

[The immunopathology mechanisms of matrix metalloproteinases in brain infection induced by parasites].

Matrix metalloproteinase (MMP) family is a class of endogenous peptidases involved in normal physiological processes of the body, such as embryonic development, wound healing, angiogenesis, cartilage absorption, etc. However, during infection, over-expression of activated matrix metalloproteinase can lead to immunopathological change, induce disease or death, also contribute to the spread or survival of pathogens. Some human parasites such as Plasmodium, Toxoplasma gondii, Cysticercus cellulose, Angiostrongylus cantonensis larvae can invade the central nervous system, and cause inflammatory response dominated by eosinophil infiltration. This article reviews function and pathological mechanism of MMP during the infection of relevant parasites involving brain.

Parasitic brain infection, endocannabinoids, and schizophrenia.

Cannabis use has often been associated with various forms of psychosis. Today it is well established that everyone produces marijuana-like compounds known as endocannabinoids. The endocannabinoid system is a homeostatic regulator of all body systems including the nervous system. As a result, imbalances in the endocannabinoid system have been considered as possible causes of various forms of mental illness and abnormal behavior. In this paper, a novel hypothesis is presented that suggests that an as yet undefined subset of schizophrenia is caused by an excess of endocannabinoids that are produced to protect the brain in response to infections by agents such as Toxoplasma gondii.

Investigação sobre a ocorrência de esquistossomose mansônica medular autóctone em uma região com baixa endemicidade(Campinas-SP) / Study on the occurrence of Schistosomiasis Mansoni in a low endemic area (Campinas, SP)

Os programas de controle da esquistossomose têm obtido relativo sucesso ao controlar a morbidade relacionada a altas cargas parasitárias desta doença, sem, no entanto, diminuir a área de transmissão no Brasil. Como a neuroesquistossomose medular á uma forma grave de esquistossomose não relacionada a altas cargas parasitárias existe risco teórico de ocorrer em áreas de baixa endemicidade. O objetivo deste estudo foi estudar a ocorrência da NE (neuroesquistossomose) medular em uma região de baixa endemicidade, região de Campinas, estado de São Paulo. Foi feito um estudo retrospectivo, descritivo de base hospitalar com busca ativa em múltiplas fontes de informação. Utilizou-se como base os dois maiores hospitais públicos da região de Campinas. Os pacientes com diagnóstico de NE medular tiveram seus diagnósticos ratificados por critérios padronizados e baseados em quadro clínico típico, comprovação da infecção por Schistosoma mansoni e exclusão de outras causas de mielopatia. Os pacientes foram classificados como autóctones, importados, sem informação e indeterminado. Após esta classificação os dados clínicos e epidemiológicos foram analisados. Foram identificados 27 pacientes com NE medular dos quais 19 (85,2%) homens e 4 (14,8%) mulheres, as idades no momento do diagnóstico foram de 13 a 57 anos (média=31,2; desvio padrão= 12,8 e mediana=29). Os pacientes foram classificados quanto ao local provável de infecção da seguinte forma: 14(51,9%) autóctones, 11(40,7%) importados e 2(7,4%) sem informações, não houve paciente classificado como indeterminado. Todos os pacientes importados se infectaram em municípios de áreas de alta endemicidade. A clínica deste grupo de pacientes não foi diferente do encontrado na literatura, nem foi diferente quando comparados os pacientes autóctones com os importados. Houve uma demora média de 70,6 dias (mediana=19; dp=166,9) entre a primeira consulta e o diagnóstico...

Programs for schistosomiasis control have enjoyed relative success in controlling death associated to high parasitary loads for this illness, without, however, decreasing the area of transmission in Brazil. Since spinal neuroschistosomiasis is a grave form of neuroschistosomiasis unrelated to high parasitary loads, there is a theoretical risk of its occurrence even when not in a particularly endemic area. The goal of this study was to study the occurrence of spinal NE (neuroschistosomiasis) in a non-endemic area, the region of Campinas, in the Sate of São Paulo. A retrospective, descriptive, hospital-based study was carried, with information actively sought after from various sources of information. The two largest public hospitals in the region of Campinas were used as bases. The patients diagnosed with spinal NE had their diagnoses ratified according to standard criteria and based on typical clinical status, proof of infection by Schistosoma mansoni and the exclusion of other causes for myelopathy. Patients were classified as autochthonous, imported, without information and undetermined. After this classification, the clinical and epidemiological data were analyzed. A total of 27 patients with spinal NE were identified, of which 19 (85.2%) were men and 4 (14.8%) women. The ages on diagnosis ranged from 13 to 57 (average=31.2; standard deviation=12.8 and median=29). The patients were classified as to their probable location of infection the following way: 14(51.9%) autochthonous, 11(40.7%) imported and 2(7.4%) without information. No patients were deemed undetermined. All imported patients were infected in municipalities located in highly endemic areas. Clinical evaluation of this group of patients was no different from that found in the literature, nor was it different when autochthonous patients were compared to imported patients. There was an average period of 70.6 days (median=19; sd=166.9) between the first consultation and diagnosis.

Onchocerciasis-related epilepsy? Prospects at a time of uncertainty.

Epilepsy and onchocerciasis (river blindness) constitute serious public health problems in several tropical countries. There are four main mechanisms that might explain a relationship between these two diseases: (i) the presence of Onchocerca volvulus in the central nervous system; (ii) the pathogenicity of various O. volvulus strains; (iii) immunological mechanisms involving cross-reactive immunization or cytokine production during infection; and (iv) the triggering role of insomnia due to itching.

Parasitic central nervous system infections in immunocompromised hosts: malaria, microsporidiosis, leishmaniasis, and African trypanosomiasis.

Immunosuppression associated with HIV infection or following transplantation increases susceptibility to central nervous system (CNS) infections. Because of increasing international travel, parasites that were previously limited to tropical regions pose an increasing infectious threat to populations at risk for acquiring opportunistic infection, especially people with HIV infection or individuals who have received a solid organ or bone marrow transplant. Although long-term immunosuppression caused by medications such as prednisone likely also increases the risk for acquiring infection and for developing CNS manifestations, little published information is available to support this hypothesis. In an earlier article published in Clinical Infectious Diseases, we described the neurologic manifestations of some of the more common parasitic CNS infections. This review will discuss the presentation, diagnosis, and treatment of the following additional parasitic CNS infections: malaria, microsporidiosis, leishmaniasis, and African trypanosomiasis.

Seroprevalence of Helicobacter pylori among children in Sana'a, Yemen.

BACKGROUND: Helicobacter pylori infection is primarily acquired in early childhood. Its transmission routes are debated. The aims of this study were to determine the seroprevalence of anti-H. pylori immunoglobulin G (IgG) in Yemeni children under 10 years of age, the potential risk factors for contracting H. pylori infection and co-infection of H. pylori with intestinal parasites. METHODS: Enzyme-labeled immunosorbent assay was used to determine the H. pylori prevalence rate among 572 healthy volunteers aged less than 10 years. Formalin ether concentration methods were used to test the prevalence of intestinal parasites (intestinal roundworms and tapeworms). In addition, we interviewed participants regarding potential risk factors for contracting H. pylori infection. RESULTS: The seroprevalence of H. pylori antibodies was 9%. The prevalence according to age varied from 0% in children under 2 years to 12.5% in age group 9-10 years. There was a correlation between the amounts of positive antibodies and increasing age. The prevalence rate of H. pylori antibodies was also significantly associated with the practice of drinking water from reused plastic jerry cans, with poor mouth hygiene and with co-infection by intestinal parasites. CONCLUSION: The prevalence of H. pylori antibodies in Yemen among children under 10 years of age is higher than that reported from other regions for the same age groups. Yemen shares some but not all potential risk factors for H. pylori infection with countries in which similar socioeconomic conditions are found. A possible way of eliminating H. pylori from the population would be via public health measures, i.e. preventing the reuse of plastic jerry cans, and improving sanitation and the standard of living.