Myeloid Cell Phenotypes in Susceptibility and Resistance to Helminth Parasite Infections

Maizels, Rick M.; Hewitson, James P.

doi:10.1128/9781555819194.ch43

Cited by 5 publications

(5 citation statements)

References 126 publications

(116 reference statements)

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“…infection. Furthermore, these data add to other discovered anti-microbial properties of sPLA 2 enzymes ( Balestrieri et al., 2009 , Degousee et al., 2002 , Koduri et al., 2002 , Maizels and Hewitson, 2016 , Weinrauch et al., 1998 ) and to the site-specific arsenal of anti-microbial responses in the small intestine ( Gallo and Hooper, 2012 ).…”

Section: Resultsmentioning

confidence: 64%

Epithelial-Cell-Derived Phospholipase A 2 Group 1B Is an Endogenous Anthelmintic

Entwistle

Pelly

Coomes

et al. 2017

Cell Host & Microbe

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SummaryImmunity to intestinal helminth infections has been well studied, but the mechanism of helminth killing prior to expulsion remains unclear. Here we identify epithelial-cell-derived phospholipase A2 group 1B (PLA2g1B) as a host-derived endogenous anthelmintic. PLA2g1B is elevated in resistant mice and is responsible for killing tissue-embedded larvae. Despite comparable activities of other essential type-2-dependent immune mechanisms, Pla2g1b−/− mice failed to expel the intestinal helminths Heligmosomoides polygyrus or Nippostrongylus brasiliensis. Expression of Pla2g1b by epithelial cells was dependent upon intestinal microbiota, adaptive immunity, and common-gamma chain-dependent signaling. Notably, Pla2g1b was downregulated in susceptible mice and inhibited by IL-4R-signaling in vitro, uncoupling parasite killing from expulsion mechanisms. Resistance was restored in Pla2g1b−/− mice by treating infective H. polygyrus L3 larvae with PLA2g1B, which reduced larval phospholipid abundance. These findings uncover epithelial-cell-derived Pla2g1b as an essential mediator of helminth killing, highlighting a previously overlooked mechanism of anti-helminth immunity.

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Section: Resultsmentioning

confidence: 64%

Epithelial-Cell-Derived Phospholipase A 2 Group 1B Is an Endogenous Anthelmintic

Entwistle

Pelly

Coomes

et al. 2017

Cell Host & Microbe

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“…Moreover, human infection with S. stercoralis is associated with lower circulating Th1 cytokines, insulin, glucagon, and the hormones adiponectin and adipsin (required for fatty acid breakdown and regulation of glucose and β ‐cell functions), all of which showed a reversal following antihelminthic treatment 156 . Similar to schistosomes, most of the STH produce antigens that induce an alternatively activated phenotype in macrophages, 157 which is necessary to contribute to the expulsion of the intestinal parasites and wound repair 156,158,159 . In the case of Trichuris suis , excretory/secretory products by themselves induce Arg1 and nitric oxide synthase 2 expression in BMDM, which highlights the phenotypic heterogeneity of macrophages in vivo and probably reflects an immunosuppressive state rather than an M2 phenotype.…”

Section: Macrophage Immunometabolism In Schistosoma and Soil‐transmitmentioning

confidence: 99%

Schistosome and intestinal helminth modulation of macrophage immunometabolism

Cortés-Selva

Fairfax

2020

Immunology

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SummaryMacrophages are fundamental to sustain physiological equilibrium and to regulate the pathogenesis of parasitic and metabolic processes. The functional heterogeneity and immune responses of macrophages are shaped by cellular metabolism in response to the host’s intrinsic factors, environmental cues and other stimuli during disease. Parasite infections induce a complex cascade of cytokines and metabolites that profoundly remodel the metabolic status of macrophages. In particular, helminths polarize macrophages to an M2 state and induce a metabolic shift towards reliance on oxidative phosphorylation, lipid oxidation and amino acid metabolism. Accumulating data indicate that helminth‐induced activation and metabolic reprogramming of macrophages underlie improvement in overall whole‐body metabolism, denoted by improved insulin sensitivity, body mass in response to high‐fat diet and atherogenic index in mammals. This review aims to highlight the metabolic changes that occur in human and murine‐derived macrophages in response to helminth infections and helminth products, with particular interest in schistosomiasis and soil‐transmitted helminths.

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“…Certain helminth infections can also elicit an alternative activation phenotype in monocytes (24). Monocyte dysfunction in helminth infections is associated with decreased capacity to express costimulatory molecules and chemokine receptors, decreased functional activity including phagocytosis, and decreased production of proinflammatory or protective cytokines (25)(26)(27). Whether any or all of these mechanisms play a role in helminth-latent TB interaction is not known.…”

Section: Discussionmentioning

confidence: 99%

Helminth Coinfection Alters Monocyte Activation, Polarization, and Function in Latent Mycobacterium tuberculosis Infection

Ray

Munisankar

Dolla

et al. 2020

The Journal of Immunology

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Helminth infections are known to influence T and B cell responses in latent tuberculosis infection (LTBI). Whether helminth infections also modulate monocyte responses in helminth-LTBI coinfection has not been fully explored. To this end, we examined the activation, polarization, and function of human monocytes isolated from individuals with LTBI with (n = 25) or without (n = 25) coincident Strongyloides stercoralis infection (S. stercoralis-positive and S. stercoralis-negative respectively). Our data reveal that the presence of S. stercoralis infection is associated with lower frequencies of monocytes expressing CD54, CD80, CD86 at baseline (absence of stimulation) and in response to mycobacterial-Ag stimulation than monocytes from S. stercoralis-negative individuals. In contrast, S. stercoralis infection was associated with higher frequencies of M2-like monocytes, as determined by expression of CD206 and CD163. Monocytes from S. stercoralis-positive individuals had a reduced capacity to phagocytose or exhibit respiratory burst activity following mycobacterial-Ag or LPS stimulation and were less capable of expression of IL-1b, TNF-a, IL-6, and IL-12 at baseline and/or following Ag stimulation compared with those without S. stercoralis infection. In addition, definitive treatment of S. stercoralis infection resulted in a significant reversal of the altered monocyte function 6 mo after anthelmintic therapy. Finally, T cells from S. stercoralis-positive individuals exhibited significantly lower activation at baseline or following mycobacterial-Ag stimulation. Therefore, our data highlight the induction of dampened monocyte activation, enhanced M2 polarization, and impaired monocyte function in helminth-LTBI coinfection. Our data also reveal a different mechanism by which helminth infection modulates immune function in LTBI.

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Myeloid Cell Phenotypes in Susceptibility and Resistance to Helminth Parasite Infections

Cited by 5 publications

References 126 publications

Epithelial-Cell-Derived Phospholipase A 2 Group 1B Is an Endogenous Anthelmintic

Epithelial-Cell-Derived Phospholipase A 2 Group 1B Is an Endogenous Anthelmintic

Schistosome and intestinal helminth modulation of macrophage immunometabolism

Helminth Coinfection Alters Monocyte Activation, Polarization, and Function in Latent Mycobacterium tuberculosis Infection

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