Immunosuppressive PAS-1 is an excretory/secretory protein released by larval and adult worms of the ascarid nematode<i>Ascaris suum</i>

Antunes, M.F.P.; Titz, T.O.; Batista, Isabel de Fátima Correia; Marques-Porto, Rafael; Oliveira, Carlos; Araújo, Claudia Andréa Alves de; Macedo-Soares, Maria Fernanda

doi:10.1017/s0022149x14000200

Cited by 16 publications

(18 citation statements)

References 56 publications

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“…There is considerable evidence of the anti-inflammatory effect of Ascaris based on the in vitro suppressive effects of Ascaris suum -derived protein (PAS-1) on pro-inflammatory cytokine production [72], the down-regulation by low intensity Ascaris infection of the IL6 response to intestinal giardiasis [73], the anti-inflammatory effect of Ascaris antigen on cytokine production by peripheral mononuclear cells from children when co-incubated with allergens [74], and the consistent protective effect of Ascaris against allergic sensitization found in a meta-analysis [75]. However, to our knowledge, this is the first report of a negative association of CRP with Ascaris during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

C-reactive protein is differentially modulated by co-existing infections, vitamin deficiencies and maternal factors in pregnant and lactating indigenous Panamanian women

et al. 2017

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BackgroundThe usefulness of C-reactive protein (CRP) as a non-specific marker of inflammation during pregnancy and lactation is unclear in impoverished populations where co-existing infections and vitamin deficiencies are common.MethodsThis cross-sectional study in Panama recruited 120 pregnant and 99 lactating Ngäbe-Buglé women from 14 communities in rural Panama. Obstetric history, indoor wood smoke exposure, fieldwork, BMI, vitamins A, B12, D, and folic acid, and inflammation markers (CRP, neutrophil/lymphocyte ratio (NLR), plateletcrit and cytokines) were measured. Multiple regressions explored both associations of CRP with other inflammatory markers and associations of CRP and elevated CRP based on trimester-specific cut-offs with maternal factors, infections and vitamin deficiencies.ResultsCRP was higher in pregnancy (51.4 ± 4.7 nmol/L) than lactation (27.8 ± 3.5 nmol/L) and was elevated above trimester specific cut-offs in 21% of pregnant and 30% of lactating women. Vitamin deficiencies were common (vitamin A 29.6%; vitamin D 68.5%; vitamin B12 68%; folic acid 25.5%) and over 50% of women had two or more concurrent deficiencies as well as multiple infections. Multiple regression models highlighted differences in variables associated with CRP between pregnancy and lactation. In pregnancy, CRP was positively associated with greater indoor wood smoke exposure, caries and hookworm and negatively associated with Ascaris and vaginal Lactobacillus and Bacteroides/Gardnerella scores. Consistent with this, greater wood smoke exposure, caries as well as higher diplococcal infection score increased the odds of trimester-elevated CRP concentrations whereas longer gestational age lowered the likelihood of a trimester-elevated CRP. During lactation, folic acid deficiency was associated with higher CRP whereas parity, number of eosinophils and Mobiluncus score were associated with lower CRP. Also, a higher BMI and Trichomonas vaginalis score increased the likelihood of an elevated CRP whereas higher parity and number of eosinophils were associated with lower likelihood of an elevated CRP.ConclusionsInfections both raise and lower CRP concentrations in pregnant and lactating mothers. Only folic acid deficiency during lactation was associated with higher CRP concentrations. Caution is required when interpreting CRP concentrations in pregnant and lactating women who have co-existing nutrient deficiencies and multiple infections.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-017-0307-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

C-reactive protein is differentially modulated by co-existing infections, vitamin deficiencies and maternal factors in pregnant and lactating indigenous Panamanian women

et al. 2017

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“…69,70 In both studies, mice were injected with 1 lg LPS with or without PCF supplementation into an air pouch and the researchers observed that helminth PCF prevented LPS-induced leukocyte influx and suppressed pro-inflammatory cytokine (IL-1b, TNF-a and IL-6) secretion. 69,70 In both studies, mice were injected with 1 lg LPS with or without PCF supplementation into an air pouch and the researchers observed that helminth PCF prevented LPS-induced leukocyte influx and suppressed pro-inflammatory cytokine (IL-1b, TNF-a and IL-6) secretion.…”

Section: Discussionmentioning

confidence: 99%

Body fluid from the parasitic worm Ascaris suum inhibits broad‐acting pro‐inflammatory programs in dendritic cells

et al. 2019

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Dendritic cells (DCs) are essential for generating T-cell-based immune responses through sensing of potential inflammatory and metabolic cues in the local environment. However, there is still limited insight into the processes defining the resultant DC phenotype, including the type of early transcriptional changes in pro-inflammatory cues towards regulatory or type 2 immune-based cues induced by a variety of exogenous and endogenous molecules. Here we compared the ability of a selected number of molecules to modulate the pro-inflammatory phenotype of lipopolysaccharide (LPS) and interferon-c (IFN-c)-stimulated human monocytederived DCs towards an anti-inflammatory or regulatory phenotype, including Ascaris suum body fluid [helminth pseudocoelomic fluid (PCF)], the metabolites succinate and butyrate, and the type 2 cytokines thymic stromal lymphopoietin and interleukin-25. Our data show that helminth PCF and butyrate treatment suppress the T helper type 1 (Th1)inducing pro-inflammatory DC phenotype through induction of different transcriptional programs in DCs. RNA sequencing indicated that helminth PCF treatment strongly inhibited the Th1 and Th17 polarizing ability of LPS + IFN-c-matured DCs by down-regulating myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways in Toll-like receptor 4 signaling. By contrast, butyrate treatment had a strong Th1-inhibiting action, and transcripts encoding important gut barrier defending factors such as IL18, IL1B and CXCL8 were up-regulated. Collectively, our results further understanding of how compounds from parasites and gut microbiota-derived butyrate may exert immunomodulatory effects on the host immune system.

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“…The immunomodulatory capacity of A. suum and A. lumbricoides components has also been studied in animal models, and some immunomodulatory components found in excretory/secretory products of Ascaris have been identified. Among them, phosphorylcholine‐containing glycosphingolipids and PAS‐1 have been more analysed; however, according to the A. suum genome, this genus might have more than 15 potential immunomodulators. In this regard, the recent analysis of the anti‐inflammatory properties of A .…”

Section: Immunological and Clinical Influences Of Ascariasis On Asthmamentioning

confidence: 99%

Ascariasis as a model to study the helminth/allergy relationships

Caraballo

Acevedo

Zakzuk

2018

Parasite Immunology

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Summary Ascariasis is the most frequent soil transmitted helminthiasis and, as well as other helminth infections, is expected to influence the clinical presentation of allergic diseases such as asthma. Indeed, several clinical and experimental works have shown an important impact either increasing or suppressing symptoms, and the same effects have been detected on the underlying immune responses. In this review we analyze the work on this field performed in Colombia, a Latin American tropical country, including aspects such as the molecular genetics of the IgE response to Ascaris; the allergenic activity of Ascaris IgE‐binding molecular components and the immunological and clinical influences of ascariasis on asthma. The analysis allows us to conclude that the impact of ascariasis on the inception and evolution of allergic diseases such as asthma deserves more investigation, but advances have been made during the last years. The concurrent parasite‐induced immunostimulatory and immunosuppressive effects during this helminthiasis do modify the natural history of asthma and some aspects of the practice of allergology in the tropics. Theoretically it can also influence the epidemiological trends of allergic diseases either by its absence or presence in different regions and countries.

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Immunosuppressive PAS-1 is an excretory/secretory protein released by larval and adult worms of the ascarid nematodeAscaris suum

Cited by 16 publications

References 56 publications

C-reactive protein is differentially modulated by co-existing infections, vitamin deficiencies and maternal factors in pregnant and lactating indigenous Panamanian women

C-reactive protein is differentially modulated by co-existing infections, vitamin deficiencies and maternal factors in pregnant and lactating indigenous Panamanian women

Body fluid from the parasitic worm Ascaris suum inhibits broad‐acting pro‐inflammatory programs in dendritic cells

Ascariasis as a model to study the helminth/allergy relationships

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