Schistosomiasis Burden and Its Association With Lower Measles Vaccine Responses in School Children From Rural Cameroon

Background and Methods: Schistosomiasis is debilitating and reported to impair immune responsiveness of infected hosts. In Cameroon, mass drug administration (MDA) is used in schoolchildren to reduce transmission of S. haematobium and S. mansoni. The effects of MDA and the impact of schistosomiasis on the titers of antibodies in vaccinated children have been poorly studied. We therefore assessed the prevalence of schistosomiasis in schoolchildren, eight months after MDA, in two locations: Barombi Koto (BK), endemic for S. haematobium (N = 169) and Yoro (Y), endemic for S. mansoni (N = 356). Age, gender, residence time and frequency of contact with river water were assessed as risk factors for infection and morbidity in both localities. In 70 schoolchildren from BK and 83 from Y, ultrasound was used to assess morbidity according to the WHO guidelines. Evaluation of measles antibodies was performed in previously vaccinated schoolchildren (14 with S. haematobium and 12 egg-negative controls from BK and 47 with S. mansoni and12 egg-negative controls from Y).Principal Findings and conclusions: The prevalence of S. haematobium was 25. 4% in BK (43/169) and 34.8% for S. mansoni in Y (124/356), indicating the persistent transmission of schistosomiasis despite MDA. Older age (AOR 1.31; 95%CI 1.12–1.54) and higher frequencies of exposure to river water (AOR 1.99; 95%CI 1.03–3.86) were identified as risks for infection in BK whereas only older age (OR 1.15; 95%CI 1.04–1.27) was a risk for infection in Y. Bladder pathology (score 2 to 5) was observed in 29.2% (7/24) of egg-positive children in BK and liver pathology (pattern C) in 31.1% (19/61) of egg-positive children in Y. There was a positive correlation between S. haematobium egg burden and bladder pathology (AOR 1.01; 95% CI 0.99–1.02) and positive correlation between S. mansoni-driven liver pathology and female gender (AOR 3.01; 95% CI 0.88–10.26). Anti-measles antibodies in vaccinated children were significantly lower in S. mansoni-infected when compared to egg-negative controls (p = 0.001), which was not observed in the S. haematobium-infected group from BK. Our results demonstrate a questionable efficacy of MDA alone in halting schistosomiasis transmission and confirm a possible immunomodulatory effect of S. mansoni on response to vaccines

Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro

Parasitic helminths are inducers of chronic diseases and have evolved mechanisms to suppress the host immune response. Mostly from studies on roundworms, a picture is currently emerging that helminths secrete factors (E/S-products) that directly act on sentinels of the immune system, dendritic cells, in order to achieve an expansion of immunosuppressive, regulatory T cells (T-reg). Parasitic helminths are currently also intensely studied as therapeutic agents against autoimmune diseases and allergies, which is directly linked to their immunosuppressive activities. The immunomodulatory products of parasitic helminths are therefore of high interest for understanding immunopathology during infections and for the treatment of allergies. The present work was conducted on larvae of the tapeworm E. multilocularis, which grow like a tumor into surrounding host tissue and thus cause the lethal disease alveolar echinococcosis. The authors found that E/S-products from early infective larvae are strong inducers of tolerogenic DC in vitro and show that E/S-products of larvae of the chronic stage lead to an in vitro expansion of Foxp3+ T cells, suggesting that both the expansion of these T cells and poorly responsive DC are important for the establishment and persistence of E. multilocularis larvae within the host

Anti-EmTIP antibody impairs <i>E. multilocularis</i> stem cell proliferation and metacestode vesicle formation <i>in vitro</i>.

<p>(<b>A</b>) Dose-response curve of the antiproliferative effect of EmTIP inhibition using affinity-purified anti-EmTIP antibody on <i>E.multilocularis</i> primary cell cultures. <i>E. multilocularis</i> stem cell proliferation was assessed by measuring the level of BrdU incorporation (see material and methods for details of the BrdU cell proliferation assay) here expressed as proliferation index. (<b>B</b>) 60 µg/ml of anti-EmTIP antibody limits <i>E. multilocularis</i> stem cell proliferation whereas an equal amount of total rabbit IgG failed to do so. (<b>C</b>) Effect of anti-EmTIP antibody (60 µg/ml) on rat hepatoma cell line proliferation. (<b>D</b>) Effect of anti-EmTIP antibody vs. rabbit IgG on the <i>de novo</i> formation of <i>E. multilocularis</i> metacestode vesicles from primary cell cultures. (<b>A, B, C</b>) Bars represent mean ± SD for 4–6 replicates of two independent experiments. (<b>D</b>) Bars stand for mean levels. Data represent 4–8 biological primary cell isolates assayed individually. ^#, statistical trend <i>p<0.1</i>;*, statistical significance <i>p<0.05</i>; NS, not significant <i>p>0.1</i>.</p

EmTIP: a T-cell immunomodulatory protein homologue from <i>E. multilocularis</i>.

<p>(<b>A</b>) Alignment of EmTIP with human and mouse TIPs. Bioedit software, version 7.0.9, was used to align the amino acids sequences. Accession numbers for the sequences are as follows: EmTIP, HF912277; human TIP, Q8TB96; mouse TIP, Q99KW9. Identical residues are displayed in white on black background, biochemically similar residues in black on grey background. Gaps introduced to maximize the alignment are represented by dashes. Numbers at the end of each line correspond to the amino acid numbers in each respective sequence. EmTIP has 36% identity/48% similarity with Human TIP and 34% identity/42% similarity with Mouse TIP. The N-terminal signal sequences are shown in an open solid black box. Two FG-GAP repeats within EmTIP as predicted by SMART (<a href="http://smart.embl-heidelberg.de/" target="_blank">http://smart.embl-heidelberg.de/</a>) are shown within open solid red boxes. The C-terminal transmembrane domains are depicted in an open solid blue box. (<b>B</b>) Comparative structural architecture of <i>E. multilocularis</i>, human and mouse T-cell immunomodulatory proteins. Red boxes: signal sequences; Grey boxes: FG-GAP repeats; Blue boxes: Transmembrane domains. Sequence accession numbers are as described in (<b>A</b>), with structural architecture predicted with SMART (<a href="http://smart.embl-heidelberg.de/" target="_blank">http://smart.embl-heidelberg.de/</a>).</p

Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis

Schistosomiasis (bilharzia) is a parasitic helminth disease that can cause severe inflammatory pathology leading to organ damage in humans. Failure of the host to regulate egg-driven granulomatous inflammation causes host morbidity during chronic infection with Schistosoma mansoni. Although the importance of B cells in regulating pathology during chronic infection has been well defined, the specific contribution of IL-4Rα-expressing B cells is still unknown. To address this, we examined B cell-specific IL-4Rα-deficient (mb1creIL-4Rα−/lox) mice in three experimental models of schistosomiasis: high-dose (100 cercariae), low dose (30 cercariae), and a synchronous egg challenge. In the high dose model, we found that mice deficient in IL-4Rα-expressing B cells were more susceptible to acute schistosomiasis than B cell-deficient (μMT) mice, succumbing to infection at the acute stage whereas μMT mice survived until the chronic stage. An S. mansoni egg challenge model demonstrated that deleting IL-4Rα expression specifically on B cells resulted in increased lung granulomatous pathology, suggesting a role for this B cell subset in controlling granulomatous pathology. In agreement with this, a low dose model of schistosomiasis—which mimics the course of clinical chronic disease—demonstrated that depleting IL-4Rα-expressing B cells in mb1creIL-4Rα−/lox mice considerably impaired the host ability to down-modulate granulomatous inflammation in the liver and gut during chronic schistosomiasis. Taken together, our findings indicate that within the B cell compartment, IL-4Rα-expressing B cells in particular down-modulate the deleterious egg-driven tissue granulomatous inflammation to enable host survival during schistosomiasis in mice.</p