Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion

Chen, Fei; El-Naccache, Darine W.; Ponessa, John J.; Lemenze, Alexander; Espinosa, Vanessa; Wu, Wenhui; Lothstein, Katherine; Jin, Linhua; Antao, Olivia Q; Weinstein, Jason S.; Damani‐Yokota, Payal; Khanna, Kamal M.; Murray, Peter J.; Rivera, Amariliz; Siracusa, Mark C.; Gause, William C.

doi:10.1016/j.celrep.2021.110215

Cited by 39 publications

(50 citation statements)

References 52 publications

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“…Specifically, NETs were found to be released upon contact with S. stercoralis larvae ( 128 ). Although the NETs failed to kill the larvae, they helped immobilize parasites ( 129 ) and may assist with “starving” the worms by trapping them in a nutrient-deficient microenvironment similar to what has recently been shown by macrophages ( 130 ). Further, Bouchery et al., showed that NETs released following an N. brasiliensis challenge can directly impair larval viability and the parasites combat this response by secreting DNAse II ( 123 ).…”

Section: The Contributions Of Neutrophils To Antihelminth Immunitymentioning

confidence: 87%

“…For instance, monocyte-derived alveolar macrophages induced post- N. brasiliensis infection are more effective at killing parasites than TRMs. The heightened ability of monocyte-derived alveolar macrophages to kill parasitic larvae was mediated by their enhanced expression of arginase 1 which allowed them to deplete local arginine ( 130 ). Further, by comparing macrophages from S. mansoni or Litomosoides sigmodontis -infected mice, along with IL-4 and anti-IL-4 antibody complexes (IL-4c) and thioglycolate-treated mice, Gundra et al.…”

Section: The Contributions Of Monocytes and Macrophages To Antihelmin...mentioning

confidence: 99%

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Communication is key: Innate immune cells regulate host protection to helminths

et al. 2022

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Parasitic helminth infections remain a significant global health issue and are responsible for devastating morbidity and economic hardships. During infection, helminths migrate through different host organs, which results in substantial tissue damage and the release of diverse effector molecules by both hematopoietic and non-hematopoietic cells. Thus, host protective responses to helminths must initiate mechanisms that help to promote worm clearance while simultaneously mitigating tissue injury. The specialized immunity that promotes these responses is termed type 2 inflammation and is initiated by the recruitment and activation of hematopoietic stem/progenitor cells, mast cells, basophils, eosinophils, dendritic cells, neutrophils, macrophages, myeloid-derived suppressor cells, and group 2 innate lymphoid cells. Recent work has also revealed the importance of neuron-derived signals in regulating type 2 inflammation and antihelminth immunity. These studies suggest that multiple body systems coordinate to promote optimal outcomes post-infection. In this review, we will describe the innate immune events that direct the scope and intensity of antihelminth immunity. Further, we will highlight the recent progress made in our understanding of the neuro-immune interactions that regulate these pathways and discuss the conceptual advances they promote.

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Section: The Contributions Of Neutrophils To Antihelminth Immunitymentioning

confidence: 87%

Section: The Contributions Of Monocytes and Macrophages To Antihelmin...mentioning

confidence: 99%

Communication is key: Innate immune cells regulate host protection to helminths

et al. 2022

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“…Most of these cells are CD206 + and co-express additional markers of the M2 phenotype ( 26 ). In contrast, inflammation promotes the influx and development of monocyte-derived airway macrophages, characterized by expression of CD11b and Siglec-F ( 35 – 37 ). Depletion of ACh reduced the M2 macrophage pool by suppressing the proportion of monocyte-derived and interstitial macrophages that displayed an M2-like phenotype and decreasing the overall number of tissue-resident airway macrophages.…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of Allergic Airway Inflammation by Acetylcholine

et al. 2022

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Acetylcholine (ACh) from neuronal and non-neuronal sources plays an important role in the regulation of immune responses and is associated with the development of several disease pathologies. We have previously demonstrated that group 2 innate lymphoid cell (ILC2)-derived ACh is required for optimal type 2 responses to parasitic infection and therefore sought to determine whether this also plays a role in allergic inflammation. RoraCre+ChatLoxP mice (in which ILC2s cannot synthesize ACh) were exposed to an allergenic extract of the fungus Alternaria alternata, and immune responses in the airways and lung tissues were analyzed. Airway neutrophilia and expression of the neutrophil chemoattractants CXCL1 and CXCL2 were enhanced 24 h after exposure, suggesting that ILC2-derived ACh plays a role in limiting excessive pulmonary neutrophilic inflammation. The effect of non-selective depletion of ACh was examined by intranasal administration of a stable parasite-secreted acetylcholinesterase. Depletion of airway ACh in this manner resulted in a more profound enhancement of neutrophilia and chemokine expression, suggesting multiple cellular sources for the release of ACh. In contrast, depletion of ACh inhibited Alternaria-induced activation of ILC2s, suppressing the expression of IL-5, IL-13, and subsequent eosinophilia. Depletion of ACh reduced macrophages with an alternatively activated M2 phenotype and an increase in M1 macrophage marker expression. These data suggest that ACh regulates allergic airway inflammation in several ways, enhancing ILC2-driven eosinophilia but suppressing neutrophilia through reduced chemokine expression.

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“…Interesting, during infection monocytes are rapidly recruited in the inflamed lung environment where they acquired an alveolar macrophage-like phenotype. These macrophages expressed SiglecF, CD11c and Arg1, and they can kill N. brasiliensis larvae in vitro possibly depleting arginine, an essential amino acid for parasite metabolism 151 .…”

Section: Helminth Infection Induced Immune Responses In the Lungmentioning

confidence: 99%

Tissue-specific immunity in helminth infections

Vacca

Gros

2022

Mucosal Immunology

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A characteristic feature of host responses to helminth infections is the development of profound systemic and tissue-localised Type 2 immune responses that play critical roles in immunity, tissue repair and tolerance of the parasite at tissue sites. These same Type 2 responses are also seen in the tissue-associated immune-pathologies seen in asthma, atopic dermatitis and many forms of allergies. The recent identification of new subtypes of immune cells and cytokine pathways that influence both immune and non-immune cells and tissues creates the opportunity for reviewing helminth parasite–host responses in the context of tissue specific immunity. This review focuses on the new discoveries of the cells and cytokines involved in tissue specific immune responses to helminths and how these contribute to host immunity against helminth infection and allow the host to accommodate the presence of parasites when they cannot be eliminated.

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Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion

Abstract: Highlights d Helminth infection promotes a restructuring of myeloid cells in the lung d Highly activated monocyte-derived macrophages populate the lung post-infection d These macrophages express alveolar macrophage markers and elevated levels of Arg1

Cited by 39 publications

References 52 publications

Communication is key: Innate immune cells regulate host protection to helminths

Communication is key: Innate immune cells regulate host protection to helminths

Differential Regulation of Allergic Airway Inflammation by Acetylcholine

Tissue-specific immunity in helminth infections

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