Microfilaria-dependent thoracic pathology associated with eosinophilic and fibrotic polyps in filaria-infected rodents.

BACKGROUND: Pulmonary manifestations are regularly reported in both human and animal filariasis. In human filariasis, the main known lung manifestations are the tropical pulmonary eosinophilia syndrome. Its duration and severity are correlated with the presence of microfilariae. Litomosoides sigmodontis is a filarial parasite residing in the pleural cavity of rodents. This model is widely used to understand the immune mechanisms that are established during infection and for the screening of therapeutic molecules. Some pulmonary manifestations during the patent phase of infection with L. sigmodontis have been described in different rodent hosts more or less permissive to infection. METHODS: Here, the permissive Mongolian gerbil (Meriones unguiculatus) was infected with L. sigmodontis. Prevalence and density of microfilariae and adult parasites were evaluated. Lungs were analyzed for pathological signatures using immunohistochemistry and 3D imaging techniques (two-photon and light sheet microscopy). RESULTS: Microfilaremia in gerbils was correlated with parasite load, as amicrofilaremic individuals had fewer parasites in their pleural cavities. Fibrotic polypoid structures were observed on both pleurae of infected gerbils. Polyps were of variable size and developed from the visceral mesothelium over the entire pleura. The larger polyps were vascularized and strongly infiltrated by immune cells such as eosinophils, macrophages or lymphocytes. The formation of these structures was induced by the presence of adult filariae since small and rare polyps were observed before patency, but they were exacerbated by the presence of gravid females and microfilariae. CONCLUSIONS: Altogether, these data emphasize the role of host-specific factors in the pathogenesis of filarial infections.

Characterizing Activation, Proliferation, and Ontogeny of Murine Macrophages in Parasitic Helminth Infections.

Helminth parasites infect approximately 1/3 of the human population. They induce a characteristic immune response whose main focus seems to be to contain the worm parasites and avoid excessive damage to the host. Macrophages are a central player in this response and research using helminth infection models has highlighted the heterogeneity of macrophage responses including distinct recruitment mechanisms, subset-specific activation profiles, and functional diversity. Thus, helminth infection models offer the excellent opportunity to analyze a unique part of the macrophage activation spectrum as well as dissect the functional contributions of macrophages to a wide variety of biologically relevant conditions like wound healing, fibrosis, and immunoregulation.As an example for the analysis of macrophages associated with helminth infection this chapter describes the isolation and magnetic enrichment of pleural macrophages from mice infected with the natural rodent parasite Litomosoides sigmodontis. In addition, it includes a detailed description of how to determine the ontogeny and proliferation status of macrophage populations in helminth infections. Although the focus of this chapter is on helminth infection-derived macrophages, the described methods can easily be adapted to other disease models.

Aspectos anatomopatológicos do parasitismo por nematódeos da superfamília filarioidea em capivaras (hydrochoerus hydrochaeris) de vida livre no Centro-Oeste brasileiro / Anatomic pathology aspects of the parasitism by cruorifilaria tuberocauda in capybaras (hydrochoerus hydrochaeris) in midwestern Brazil

São descritos dois casos de parasitismo por Cruorifilaria tuberocauda em capivaras de vida livre no Distrito Federal, Brasil. Macroscopicamente, observou-se nas superfícies de corte dos rins espessamento acentuado de vasos das regiões cortical e córtico-medular. Microscopicamente, havia arterite proliferativa e granulomatosa acentuada associada a filarídeos intralesionais consistentes com Cruorifilaria tuberocauda. Esse é o primeiro relato do parasitismo por esse filarídeo em capivaras no Distrito Federal.

This report describes two cases of parasitism by Cruorifilaria tuberocauda in wild capybaras (Hydrochoerus hydrochaeris) from Distrito Federal, Brazil. Grossly, there was marked thickening of vessels wall of the cortical and corticomedullary regions of both kidneys. Microscopically, there was severe proliferative and granulomatous arteritis associated with intralesional filarids, consistent with Cruorifilaria tuberocauda. For the first time this filarid is reported parasitizing capybaras in Distrito Federal, Brazil.

Neurological manifestations of filarial infections.

Filarial infections cause a huge public health burden wherever they are endemic. These filaria may locate anywhere in the human body. Their manifestations and pathogenic mechanisms, except the most common ones, are rarely investigated systematically. Their neurological manifestations, however, are being increasingly recognized particularly with onchocerciasis or Loa loa infections, Wuchereria bancrofti, or Mansonella perstans. The risk of developing these manifestations may also increase in cases that harbor multiple filariasis or coinfections, for instance as with Plasmodium. The microfilaria of Onchocerca and Loa loa are seen in cerebrospinal fluid. The pathogenesis of neurological manifestations of these infections is complex; however, pathogenic reactions may be caused by mechanical disruption, e.g., degeneration often followed by granulomas, causing fibrosis or mass effects on other tissues, vascular lesions, e.g., vascular block of cerebral vessels, or disordered inflammatory responses resulting in meningitis, encephalitis or localized inflammatory responses. The chances of having neurological manifestations may also depend upon the frequency and"heaviness"of infection over a lifetime. Hence, this type of infection should no longer be considered a disease of the commonly affected areas but one that may produce systemic effects or other manifestations, and these should be considered in populations where they are endemic.

Chronic helminth infection does not exacerbate Mycobacterium tuberculosis infection.

BACKGROUND: Chronic helminth infections induce a Th2 immune shift and establish an immunoregulatory milieu. As both of these responses can suppress Th1 immunity, which is necessary for control of Mycobacterium tuberculosis (MTB) infection, we hypothesized that chronic helminth infections may exacerbate the course of MTB. METHODOLOGY/PRINCIPAL FINDINGS: Co-infection studies were conducted in cotton rats as they are the natural host for the filarial nematode Litomosoides sigmodontis and are an excellent model for human MTB. Immunogical responses, histological studies, and quantitative mycobacterial cultures were assessed two months after MTB challenge in cotton rats with and without chronic L. sigmodontis infection. Spleen cell proliferation and interferon gamma production in response to purified protein derivative were similar between co-infected and MTB-only infected animals. In contrast to our hypothesis, MTB loads and occurrence and size of lung granulomas were not increased in co-infected animals. CONCLUSIONS/SIGNIFICANCE: These findings suggest that chronic filaria infections do not exacerbate MTB infection in the cotton rat model. While these results suggest that filaria eradication programs may not facilitate MTB control, they indicate that it may be possible to develop worm-derived therapies for autoimmune diseases that do not substantially increase the risk for infections.

A rare case of giant leiomyosarcoma in a filarial scrotum: a case report.

Giant leiomyosarcoma of scrotum is a rare tumour. A case of scrotum leiomyosarcoma is presented in a 67 year old patient with scrotal filariasis which was managed successfully with total scrotectomy with bilateral orchidectomy, degloved penis reconstructed with rotation advancement supra pubic fasciocutaneous flap. We made a literature search proving the rarity of this lesion type. Only 36 cases have been described and the first case in a filarial scrotum.

Pleural cellular reaction to the filarial infection Litomosoides sigmodontis is determined by the moulting process, the worm alteration, and the host strain.

The filarial nematode Litomosoides sigmodontis model was used to decipher the complex in vivo relationships between filariae, granulomas and leukocytes in the host's pleural cavity. The study was performed from D5 p.i.: to D47 p.i. in resistant C57BL/6 mice, to D74 p.i. in susceptible BALB/c mice, and to D420 p.i. in permissive jirds. We showed that, during the first month, leukocytes only clustered as granulomas around shed cuticles (exuviae) and with eosinophils as the major constituents. In addition, carbohydrates residues became abundant on exuviae only, suggesting a glycan-dependent mechanism of eosinophil attachment. Neutrophils were absent from the pleural cavity of all rodents and from the murine granulomas, but they made up 25% of the granuloma cell population in jirds. After the first month of infection granulomas formed around developed adult worms and morphological evidence suggested that leukocytes preferentially clustered around altered, but still motile, worms. No carbohydrates were detected on these worms and neutrophils were abundant in those granulomas. Finally, a rare third type of granuloma was observed in the resistant mice only; they contained young newly moulted adult worms; typically these granulomas were attached to the lateral lines of the worm via eosinophils; this feature correlated with the persistence of carbohydrate residues on the worms' lateral lines. Neutrophils were always in low proportion in all granulomas from resistant mice, suggesting difference in their adhesive properties in these mice. In vitro neutrophil recruitment in resistant mice was similar to that observed in susceptible mice although they expressed less cell surface CD11b.

Removal of regulatory T cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo.

Human filarial parasites cause chronic infection associated with long-term down-regulation of the host's immune response. We show here that CD4+ T cell regulation is the main determinant of parasite survival. In a laboratory model of infection, using Litomosoides sigmodontis in BALB/c mice, parasites establish for >60 days in the thoracic cavity. During infection, CD4+ T cells at this site express increasing levels of CD25, CTLA-4, and glucocorticoid-induced TNF receptor family-related gene (GITR), and by day 60, up to 70% are CTLA-4(+)GITR(high), with a lesser fraction coexpressing CD25. Upon Ag stimulation, CD4(+)CTLA-4(+)GITR(high) cells are hyporesponsive for proliferation and cytokine production. To test the hypothesis that regulatory T cell activity maintains hyporesponsiveness and prolongs infection, we treated mice with Abs to CD25 and GITR. Combined Ab treatment was able to overcome an established infection, resulting in a 73% reduction in parasite numbers (p < 0.01). Parasite killing was accompanied by increased Ag-specific immune responses and markedly reduced levels of CTLA-4 expression. The action of the CD25(+)GITR+ cells was IL-10 independent as in vivo neutralization of IL-10R did not restore the ability of the immune system to kill parasites. These data suggest that regulatory T cells act, in an IL-10-independent manner, to suppress host immunity to filariasis.

Electron microscopic observation of eosinophils migrated to the thoracic cavity of Litomosoides carinii-infected mice.

In order to study the role of eosinophils in filarial infection, ddY mice were inoculated with 20 Litomosoides carinii 7-day larvae each by the artificial pneumothorax technique. Migrated cells and larvae were collected from the thoracic cavity of the infected mice weekly from the 1st to the 8th week after infection and prepared for transmission electron microscopic observation. The number of migrated eosinophils and the proportion of eosinophils in the total migrated cells reached a peak at the 5th week. At the same time, eosinophils with low density granules were observed in both unattached and attached cells. In particular, many attached eosinophils with low density granules were observed directly on the worm surface. These observations strongly suggest that eosinophils are associated with attack on filarial worms.

"Larva currens": relato de dois casos / \"Larva currens\": two case report

O autor relata dois casos de erupçäo cutânea, extremamente pruriginosa, com eosinofilia importante e concomitante com infestaçäo por S.stercoralis (Larva currens).

Hemocyte monophenol oxidase activity in mosquitoes exposed to microfilariae of Dirofilaria immitis.

Monophenol oxidase (MPO) activity in hemocytes collected from Aedes aegypti Liverpool strain and Aedes trivittatus intrathoracically inoculated with saline alone, inoculated with Dirofilaria immitis microfilariae (mff), or from uninoculated mosquitoes was compared using a radiometric tyrosine hydroxylation assay. Hemocyte MPO activity in mff-inoculated (= immune-activated) mosquitoes was significantly increased at 24 hr postinoculation (PI) in A. aegypti and at 6, 12, and 24 hr PI in A. trivittatus as compared with saline-inoculated controls. Baseline and immune-activated levels of hemocyte MPO activity in A. trivittatus were significantly higher compared with those seen in A. aegypti. Baseline hemocyte population levels were similar in both species, but immune activation did not elicit increases in total hemocyte populations in A. trivittatus as has been demonstrated for A. aegypti. Likewise, immune activation by the inoculation of mff did not significantly alter plasma MPO activity in A. trivittatus as compared with uninoculated or saline-inoculated mosquitoes. Plasma MPO activity in A. aegypti, however, appears to constitute a major component of the immune response. The importance of phenol oxidase(s) in the immune response of mosquitoes against mff and the relationship of observed differences in MPO activity to differences in immunological capability between A. aegypti and A. trivittatus are assessed.