Genetic Background Affects the Mucosal Secretory IgA Levels, Parasite Burden, Lung Inflammation, and Mouse Susceptibility to<i>Ascaris suum</i>Infection

Oliveira, Luciana M.; Nogueira, Denise Silva; Geraldi, Ricardo Marcelo; Barbosa, Fernando Sérgio; Amorim, Chiara Cássia Oliveira; Gazzinelli-Guimarães, Ana Clara; Resende, Nathália Maria; Pinheiro-Rosa, Natália; Kraemer, Lucas; Mattos, Matheus Silvério; Bueno, Lilian Lacerda; Faria, Ana Maria Caetano; Russo, Remo Castro; Gaze, Soraya; Fujiwara, Ricardo Toshio

doi:10.1128/iai.00595-21

Cited by 4 publications

(1 citation statement)

References 69 publications

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“…The differences in hepatic and pulmonary larval load were therefore apparently not due to unequal efficiency in the invasion of the intestinal barrier by Ascaris L3, but likely due to differences in migration behavior, whereby substrain-specific differences (CBA/Ca in previous studies vs. CBA/JR in our study) could be relevant here. A recent comparative study in Ascaris -infected BALB/c and C57BL/6J mice showed a correlation between higher concentrations of total sIgA in the intestinal fluid and a lower parasite load in the more resistant BALB/c mice 48 . Thus, a comparison of the sIgA levels also for CBA and C57BL/6 mice might represent a valuable addition for future studies examining the intrinsic resistance mechanisms to larval ascariasis.…”

Section: Discussionmentioning

confidence: 94%

Th2-biased immune responses to body migrating Ascaris larvae in primary infection are associated with pathology but not protection

Elizalde-Velázquez,

Schlosser-Brandenburg,

Laubschat

et al. 2024

Sci Rep

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Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae are responsible for the unequal distribution of worms in natural host populations and thus investigated a susceptible versus a resistant mouse strain. In mice, the roundworm larvae develop until the lung stage and thus early anti-Ascaris immune responses against the migrating larvae in the liver and lung can be deciphered. Our data show that susceptible C57BL/6 mice respond to Ascaris larval migration significantly stronger compared to resistant CBA mice and the anti-parasite reactivity is associated with pathology. Increased eosinophil recruitment was detected in the liver and lungs, but also in the spleen and peritoneal cavity of susceptible mice on day 8 post infection compared to resistant mice. In serum, eosinophil peroxidase levels were significantly higher only in the susceptible mice, indicating functional activity of the recruited eosinophils. This effect was associated with an increased IL-5/IL-13 production by innate lymphoid cells and CD4+ T cells and a pronounced type 2 macrophage polarization in the lungs of susceptible mice. Furthermore, a comparison of wildtype BALB/c and eosinophil-deficient dblGATA-1 BALB/c mice showed that eosinophils were not essential for the early control of migrating Ascaris larvae. In conclusion, in primary infection, a strong local and systemic type 2 immune response during hepato-tracheal helminth larval migration is associated with pathology rather than protection.

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Section: Discussionmentioning

confidence: 94%

Th2-biased immune responses to body migrating Ascaris larvae in primary infection are associated with pathology but not protection

Elizalde-Velázquez,

Schlosser-Brandenburg,

Laubschat

et al. 2024

Sci Rep

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Role of mucosal IgA antibodies as novel therapies to enhance mucosal barriers

Gao,

Morita,

Shinkura

2024

Semin Immunopathol

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To prevent infection, the experience of the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic has led to recognition of the importance of not only vaccines but also the strengthening of mucosal barriers by secretory immunoglobulin A (IgA). Strong mucosal barrier provided by IgA is also possible to prevent allergies and chronic inflammatory conditions in the intestinal tract, since it can protect foreign enemies or antigens at the first line of defense before their invasion. Therefore, it is important to understand the role of IgA antibodies secreted by the mucosa of the body. In this section, we discuss the role of mucosal IgA antibodies in relation to three disease states: control of intestinal microbiota, protection against infection, and allergy. In addition, we provide the evidence in which the quality as well as the quantity of IgA is critical for disease prevention. Therefore, we discuss about novel strategies to enhance mucosal barriers by induction of high-quality IgA.

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In silico design of a polypeptide as a vaccine candidate against ascariasis

Evangelista

Vliet

Lawton

et al. 2023

Sci Rep

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Ascariasis is the most prevalent zoonotic helminthic disease worldwide, and is responsible for nutritional deficiencies, particularly hindering the physical and neurological development of children. The appearance of anthelmintic resistance in Ascaris is a risk for the target of eliminating ascariasis as a public health problem by 2030 set by the World Health Organisation. The development of a vaccine could be key to achieving this target. Here we have applied an in silico approach to design a multi-epitope polypeptide that contains T-cell and B-cell epitopes of reported novel potential vaccination targets, alongside epitopes from established vaccination candidates. An artificial toll-like receptor-4 (TLR4) adjuvant (RS09) was added to improve immunogenicity. The constructed peptide was found to be non-allergic, non-toxic, with adequate antigenic and physicochemical characteristics, such as solubility and potential expression in Escherichia coli. A tertiary structure of the polypeptide was used to predict the presence of discontinuous B-cell epitopes and to confirm the molecular binding stability with TLR2 and TLR4 molecules. Immune simulations predicted an increase in B-cell and T-cell immune response after injection. This polypeptide can now be validated experimentally and compared to other vaccine candidates to assess its possible impact in human health.

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Genetic Background Affects the Mucosal Secretory IgA Levels, Parasite Burden, Lung Inflammation, and Mouse Susceptibility toAscaris suumInfection

Cited by 4 publications

References 69 publications

Th2-biased immune responses to body migrating Ascaris larvae in primary infection are associated with pathology but not protection

Th2-biased immune responses to body migrating Ascaris larvae in primary infection are associated with pathology but not protection

Role of mucosal IgA antibodies as novel therapies to enhance mucosal barriers

In silico design of a polypeptide as a vaccine candidate against ascariasis

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