Chronicity in Strongyloides stercoralis infections: dichotomy of the protective immune response to infective and autoinfective larvae in a mouse model.

Strongyloidiasis is an intestinal disease that can last for decades due to the occurrence of autoinfective larvae (L3a) in an infected person, which contribute to the maintenance of the population of adult worms in the intestine. The goal of the present study was to determine if L3a are susceptible to the protective immunity that targets the infective stage of the worm, the third-stage larvae (L3). Mice immunized and challenged with Strongyloides stercoralis L3 kill more than 90% of challenge larvae contained within diffusion chambers. The L3 do not remain antigenically static in mice, however, but undergo some degree of antigenic change before they are killed, becoming host-activated larvae (L3+). The L3/L3+ are killed in this model system by the combined effects of both parasite-specific IgM and eosinophils. Mice immunized with L3 were able to kill L3/L3+, but did not kill L3a, in challenge infections. Eosinophils were, however, present in diffusion chambers containing L3a, and IgM bound to the surface of L3a. We hypothesized that differential IgM recognition of soluble L3a, L3, and L3+ antigens is the reason why the immune response generated against L3 could not kill L3a. Many common antigens on L3, L3+, and L3a were recognized by serum from mice immunized with L3, as determined by immunoblotting. However, several unique L3, L3+, and L3a antigens were also recognized by immune serum, thus indicating that antigen recognition with IgM antibodies is different between the L3, L3+, and L3a stages. This difference in antigen recognition could explain why L3a are able to evade the immune response that targets L3/L3+ in chronically infected hosts

Intestinal strongyloidiasis and hyperinfection syndrome

In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis, has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection. Th(2 )cell-mediated immunity, humoral immunity and mucosal immunity have been shown to have protective effects against this parasitic infection especially in animal models. Any factors that suppress these mechanisms (such as intercurrent immune suppression or glucocorticoid therapy) could potentially trigger hyperinfection or disseminated infection which could be fatal. Even with the recent advances in laboratory tests, strongyloidiasis is still difficult to diagnose. But once diagnosed, the disease can be treated effectively with antihelminthic drugs like Ivermectin. This review article summarizes a case of strongyloidiasis and various aspects of strongyloidiasis, with emphasis on epidemiology, life cycle of Strongyloides stercoralis, clinical manifestations of the disease, corticosteroids and strongyloidiasis, diagnostic aspects of the disease, various host defense pathways against strongyloidiasis, and available treatment options

Interactions Of Porphyrins And Metalloporphyrins With Single-Stranded Poly(dA)

A study of the interactions of single-stranded poly(deoxyadenylic acid) (poly(dA)) with a number of metallo- and nonmetallo-porphyrins is reported. Among the metal derivatives considered is the newly synthesized platinum(II) complex of tetrakis(N-methylpyridinium-4-yl)porphine (PtTMpyP-4). This metalloporphyrin behaves like other four-coordinated species in that it intercalates into double-stranded (ds) calf thymus DNA, resulting in a large bathochromic shift (18 nm) and hypochromicity (46%) of its Soret maximum. In addition, an induced, negative circular dichroism (CD) feature, typical of porphyrin intercalators, is observed at 420 nm with a Δε of -13 M⁻¹ cm⁻¹. All the porphyrin⋅poly(dA) complexes studied yield considerable hypochromicity compared to the free porphyrin, suggesting extensive interaction of the π-system of the porphyrins with that of the adenine bases. Whereas intercalating porphyrins display a hypochromicity with poly(dA) that is comparable to that obtained with calf thymus (ct) DNA, ZnTMpyP-4, which is a groove-binder by virtue of its single-axial ligand (H₂O), produces a substantially greater hypochromicity with the single-stranded than with the double-stranded nucleic acid. These results are consistent with a pseudointercalation model for binding of porphyrins to poly(dA). In addition, undercertain conditions CuTMpyP-4⋅poly(dA) shows a large conservative CD feature in the Soret region (Δε ~ ±10² M−¹ cm−¹), unlike profiles observed for other CuTMpyP-4⋅nucleic acid complexes. This metalloporphyrin may by virtue of this CD signature prove to be a useful reagent in reporting the presence of single-stranded regions in a complex nucleic acid mixture