Abstract
BackgroundParasitic infections can increase susceptibility to bacterial co-infections. This may be true for urogenital schistosomiasis and bacterial urinary tract co-infections (UTI). We previously reported that this co-infection is facilitated by S. haematobium eggs triggering interleukin-4 (IL-4) production and sought to dissect the underlying mechanisms. The interleukin-4-inducing principle from Schistosoma mansoni eggs (IPSE) is one of the most abundant schistosome egg-secreted proteins and binds to IgE on the surface of basophils and mast cells to trigger IL-4 release. IPSE can also translocate into host nuclei using a nuclear localization sequence (NLS) to modulate host transcription. We hypothesized that IPSE is the factor responsible for the ability of S. haematobium eggs to worsen UTI pathogenesis.MethodsMice were intravenously administered a single 25 μg dose of recombinant S. haematobium-derived IPSE, an NLS mutant of IPSE or PBS. Following IPSE exposure, mice were serially weighed and organs analyzed by histology to assess for toxicity. Twenty-four hours after IPSE administration, mice were challenged with the uropathogenic E. coli strain UTI89 by urethral catheterization. Bacterial CFU were measured using urine. Bladders were examined histologically for UTI-triggered pathogenesis and by PCR for antimicrobial peptide and pattern recognition receptor expression.ResultsUnexpectedly, IPSE administration did not result in significant differences in urine bacterial CFU. However, IPSE administration did lead to a significant reduction in UTI-induced bladder pathogenesis and the expression of anti-microbial peptides in the bladder. Despite the profound effect of IPSE on UTI-triggered bladder pathogenesis and anti-microbial peptide production, mice did not demonstrate systemic ill effects from IPSE exposure.ConclusionsOur data show that IPSE may play a major role in S. haematobium-associated urinary tract co-infection, albeit in an unexpected fashion. These findings also indicate that IPSE either works in concert with other IL-4-inducing factors to increase susceptibility of S. haematobium-infected hosts to bacterial co-infection or does not contribute to enhancing vulnerability to this co-infection.Graphical
Highlights
Parasitic infections can increase susceptibility to bacterial co-infections
inducing principle of Schistosoma mansoni eggs (IPSE) does not alter susceptibility to urinary tract co-infections (UTI) In prior work we have demonstrated that a single injection of S. haematobium eggs into the bladder walls of otherwise UTI-resistant BALB/c mice renders them much more sensitive to UTI [19]
A high intravenous dose of H-IPSE (25 μg, Fig. 1) did not enhance vulnerability of mice to transurethral infection with the uropathogenic UTI89 E. coli strain. This was true over an entire week of daily urine sampling, and a nuclear localization sequence (NLS)-deficient mutant of H-IPSE did not alter UTI susceptibility in mice
Summary
Parasitic infections can increase susceptibility to bacterial co-infections. This may be true for urogenital schistosomiasis and bacterial urinary tract co-infections (UTI). The main schistosomes affecting humans include Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum, with S. haematobium comprising the majority of infections All three of these species secrete immunomodulatory proteins, such as omega-1 [2], kappa-5 [3], SJHME-1 [4], Sj16 [5], and the interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE) [6], called α-1 [7]. These immunomodulatory products of schistosomes have been postulated to exert far-reaching regulatory effects on host responses to schistosomiasis, and co-infections. Another member of Enterobacteriaceae that may co-infect large numbers of patients with schistosomiasis is E. coli
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