Chronic Salmonellosis, Urinary Schistosomiasis, and Massive Proteinuria *

Farid, Z.; Higashi, Gene I.; Bassily, S.; Young, Stuart W.; Sparks, Henry A.

doi:10.4269/ajtmh.1972.21.578

“…Schistosomiasis is co-endemic with many other pathogens, including Plasmodium (31), HIV (31), mycobacteria (32), other helminths and parasites (33), and also Enterobacteriaceae such as Salmonella (34). Another member of Enterobacteriaceae that may co-infect large numbers of patients with schistosomiasis is E. coli.…”

Section: Discussionmentioning

confidence: 99%

IPSE, a Urogenital Parasite-Derived Immunomodulatory Molecule, Suppresses Bladder Pathogenesis and Anti-Microbial Peptide Gene Expression in Bacterial Urinary Tract Co-Infection

Mbanefo

¹

,

Le²,

Pennington

³

et al. 2020

Preprint

0

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Background: Parasitic 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. Methods: Mice were intravenously administered a single 25 mg 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 expression.Results: Unexpectedly, 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.Conclusions: Our 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.

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“…These immunomodulatory products of schistosomes have been postulated to exert far-reaching regulatory effects on host responses not only to schistosomiasis, but also co-infections. Schistosomiasis is co-endemic with many other pathogens, including Plasmodium [8], HIV [8], mycobacteria [9], other helminths and parasites [10], and also Enterobacteriaceae such as Salmonella [11]. Another member of Enterobacteriaceae that may co-infect large numbers of patients with schistosomiasis is E. coli.…”

Section: Introductionmentioning

confidence: 99%

IPSE, a urogenital parasite-derived immunomodulatory molecule, suppresses bladder pathogenesis and anti-microbial peptide gene expression in bacterial urinary tract infection

Mbanefo

¹

,

Le

²

,

Pennington

³

et al. 2020

View full text Add to dashboard Cite

Background Parasitic 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. Methods Mice 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. Results Unexpectedly, 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. Conclusions Our 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.

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“…These immunomodulatory products of schistosomes have been postulated to exert far-reaching regulatory effects on host responses to not only schistosomiasis, but also co-infections. Schistosomiasis is co-endemic with many other pathogens, including Plasmodium (8), HIV (8), mycobacteria (9), other helminths and parasites (10), and also Enterobacteriaceae such as Salmonella (11). Another member of Enterobacteriaceae that may co-infect large numbers of patients with schistosomiasis is E. coli.…”

Section: Introductionmentioning

confidence: 99%

IPSE, a Urogenital Parasite-Derived Immunomodulatory Molecule, Suppresses Bladder Pathogenesis and Anti-Microbial Peptide Gene Expression in Bacterial Urinary Tract Infection

Mbanefo

¹

,

Le²,

Pennington

³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Background: Parasitic 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. Methods: Mice were intravenously administered a single 25 mg 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 expression.Results: Unexpectedly, 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.Conclusions: Our 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.

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Chronic Salmonellosis, Urinary Schistosomiasis, and Massive Proteinuria *

Cited by 25 publications

References 0 publications

IPSE, a Urogenital Parasite-Derived Immunomodulatory Molecule, Suppresses Bladder Pathogenesis and Anti-Microbial Peptide Gene Expression in Bacterial Urinary Tract Co-Infection

IPSE, a Urogenital Parasite-Derived Immunomodulatory Molecule, Suppresses Bladder Pathogenesis and Anti-Microbial Peptide Gene Expression in Bacterial Urinary Tract Co-Infection

IPSE, a urogenital parasite-derived immunomodulatory molecule, suppresses bladder pathogenesis and anti-microbial peptide gene expression in bacterial urinary tract infection

IPSE, a Urogenital Parasite-Derived Immunomodulatory Molecule, Suppresses Bladder Pathogenesis and Anti-Microbial Peptide Gene Expression in Bacterial Urinary Tract Infection

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