Alterations in Peripheral Blood B Cell Subsets and Dynamics of B Cell Responses during Human Schistosomiasis

Antibody responses are thought to play an important role in control of Schistosoma infections, yet little is known about the phenotype and function of B cells in human schistosomiasis. We set out to characterize B cell subsets and B cell responses to B cell receptor and Toll-like receptor 9 stimulation in Gabonese schoolchildren with Schistosoma haematobium infection. Frequencies of memory B cell (MBC) subsets were increased, whereas naive B cell frequencies were reduced in the schistosome-infected group. At the functional level, isolated B cells from schistosome-infected children showed higher expression of the activation marker CD23 upon stimulation, but lower proliferation and TNF-α production. Importantly, 6-months after 3 rounds of praziquantel treatment, frequencies of naive B cells were increased, MBC frequencies were decreased and with the exception of TNF-α production, B cell responsiveness was restored to what was seen in uninfected children. These data show that S. haematobium infection leads to significant changes in the B cell compartment, both at the phenotypic and functional level

Schistosomes Induce Regulatory Features in Human and Mouse CD1dhi B Cells: Inhibition of Allergic Inflammation by IL-10 and Regulatory T Cells

Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, Schistosoma mansoni-mediated protection against experimental ovalbumin-induced allergic airway inflammation (AAI) was shown to be specifically dependent on IL-10-producing B cells. To study the organs involved, we transferred B cells from lungs, mesenteric lymph nodes or spleen of OVA-infected mice to recipient OVA-sensitized mice, and showed that both lung and splenic B cells reduced AAI, but only splenic B cells in an IL-10-dependent manner. Although splenic B cell protection was accompanied by elevated levels of pulmonary FoxP3+ regulatory T cells, in vivo ablation of FoxP3+ T cells only moderately restored AAI, indicating an important role for the direct suppressory effect of regulatory B cells. Splenic marginal zone CD1d+ B cells proved to be the responsible splenic B cell subset as they produced high levels of IL-10 and induced FoxP3+ T cells in vitro. Indeed, transfer of CD1d+ MZ-depleted splenic B cells from infected mice restored AAI. Markedly, we found a similarly elevated population of CD1dhi B cells in peripheral blood of Schistosoma haematobium-infected Gabonese children compared to uninfected children and these cells produced elevated levels of IL-10. Importantly, the number of IL-10-producing CD1dhi B cells was reduced after anti-schistosome treatment. This study points out that in both mice and men schistosomes have the capacity to drive the development of IL-10-producing regulatory CD1dhi B cells and furthermore, these are instrumental in reducing experimental allergic inflammation in mice

Randomized, Controlled, Assessor-Blind Clinical Trial To Assess the Efficacy of Single-versus Repeated-Dose Albendazole To Treat Ascaris lumbricoides, Trichuris trichiura,and Hookworm Infection

In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.

Alterations in Peripheral Blood B Cell Subsets and Dynamics of B Cell Responses during Human Schistosomiasis

<div><p>Antibody responses are thought to play an important role in control of <i>Schistosoma</i> infections, yet little is known about the phenotype and function of B cells in human schistosomiasis. We set out to characterize B cell subsets and B cell responses to B cell receptor and Toll-like receptor 9 stimulation in Gabonese schoolchildren with <i>Schistosoma haematobium</i> infection. Frequencies of memory B cell (MBC) subsets were increased, whereas naive B cell frequencies were reduced in the schistosome-infected group. At the functional level, isolated B cells from schistosome-infected children showed higher expression of the activation marker CD23 upon stimulation, but lower proliferation and TNF-α production. Importantly, 6-months after 3 rounds of praziquantel treatment, frequencies of naive B cells were increased, MBC frequencies were decreased and with the exception of TNF-α production, B cell responsiveness was restored to what was seen in uninfected children. These data show that <i>S. haematobium</i> infection leads to significant changes in the B cell compartment, both at the phenotypic and functional level.</p> </div

Atypical MBC analysis.

<p>PBMC were fixed and stained with B cell phenotyping markers (CD19, CD21 and CD27) and analyzed for B cell subsets by flow cytometry. B cell subset analysis was performed as shown in (A) (representative <i>S. haematobium-</i>uninfected child). Proportion of CD19-gated cells that were CD27⁺CD21⁻ (B, activated MBC), CD27⁺CD21⁺ (C, classical MBC), CD27⁻CD21⁻ (D, atypical MBC), and CD27⁻CD21⁺ (E, naive B cells) were determined for <i>S. haematobium-</i>infected and uninfected children at baseline and follow-up. (B, C, D, E) Horizontal bars represent median. Number of donors in each group: baseline <i>S.h.</i> −ve n = 19, baseline <i>S.h.</i> +ve n = 20, follow-up <i>S.h.</i> −ve n = 8 and follow-up <i>S.h.</i> +ve n = 7.</p

Serum immunoglobulin analysis.

<p>Serum samples were analyzed for total human IgM, IgG1, IgG2, IgG3, IgG4, IgA by Luminex and IgE by ELISA. Bars represent median with interquartile range. Number of donors in each group: baseline <i>S.h.</i> −ve n = 9, baseline <i>S.h.</i> +ve n = 10, follow-up <i>S.h.</i> −ve n = 8 and follow-up <i>S.h.</i> +ve n = 7.</p

MBC analysis.

<p>PBMC were fixed and stained with B cell phenotyping markers (CD19, CD27 and IgD) and analyzed for B cell subsets by flow cytometry. B cell subset analysis was performed as shown in (A) (representative <i>S. haematobium-</i>uninfected child). Proportion of CD19-gated cells that were CD27⁺IgD⁻ (B, switched MBC), CD27⁺IgD⁺ (C, non-switched MBC), CD27⁻IgD⁻ (D, double negative MBC), and CD27⁻IgD⁺ (E, naive B cells) were determined for <i>S. haematobium</i>-infected and uninfected children at baseline and follow-up. (B, C, D, E) Horizontal bars represent median. Number of donors in each group: baseline <i>S.h.</i> −ve n = 19, baseline <i>S.h.</i> +ve n = 21, follow-up <i>S.h.</i> −ve n = 8 and follow-up <i>S.h.</i> +ve n = 7.</p