Granulocytes: effector cells or immunomodulators in the immune response to helminth infection?

Cadman, Emma T.; Lawrence, Rachel A.

doi:10.1111/j.1365-3024.2009.01147.x

Cited by 46 publications

(40 citation statements)

References 200 publications

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“…Although both these cell types are implicated in the resolution of a number of helminth infections, 27 -29 their roles in N. brasiliensis immunity is limited. 30 These results extend previous observations by us that in vivo IL-4R -responsive smooth muscle cells are beneficial for N. brasiliensis expulsion by coordinating T H 2 cytokine responses, goblet cell hyperplasia, and M3 receptor expression in the intestine, all of which are potential mediators of worm expulsion . 17 Together, with the current data, a more general role for smooth muscle cell IL-4R signaling in the onset of local immune responses and the development of T H 2 responses following N. brasiliensis infection is apparent.…”

Section: Discussionsupporting

confidence: 89%

IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

et al. 2011

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Nippostrongylus brasiliensis infections generate pulmonary pathologies that can be associated with strong T(H)2 polarization of the host's immune response. We present data demonstrating N. brasiliensis-driven airway mucus production to be dependent on smooth muscle cell interleukin 4 receptor-α (IL-4Rα) responsiveness. At days 7 and 10 post infection (PI), significant airway mucus production was found in IL-4Rα(-/lox) control mice, whereas global knockout (IL-4Rα(-/-)) and smooth muscle-specific IL-4Rα-deficient mice (SM-MHC(Cre) IL-4Rα(-/lox)) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHC(Cre) IL-4Rα(-/lox) mice was impaired along with a transient reduction in T-cell numbers in the lung. In vitro treatment of smooth muscle cells with secreted N. brasiliensis excretory-secretory antigen (NES) induced IL-6 production. Decreased protein kinase C (PKC)-dependent smooth muscle cell proliferation associated with cell cycle arrest was found in cells stimulated with NES. Together, these data demonstrate that both IL-4Rα and NES-driven responses by smooth muscle cells make important contributions in initiating T(H)2 responses against N. brasiliensis infections.

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Section: Discussionsupporting

confidence: 89%

IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

et al. 2011

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“…Primary or secondary protective immune responses to helminths comprise many specific interactions of host cells and molecules (5). In particular, both eosinophils and neutrophils have been identified to be effector and immunomodulatory cells during helminth infections (14).…”

mentioning

confidence: 99%

Major Basic Protein from Eosinophils and Myeloperoxidase from Neutrophils Are Required for Protective Immunity to Strongyloides stercoralis in Mice

et al. 2011

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Eosinophils and neutrophils contribute to larval killing during the primary immune response, and neutrophils are effector cells in the secondary response to Strongyloides stercoralis in mice. The objective of this study was to determine the molecular mechanisms used by eosinophils and neutrophils to control infections with S. stercoralis. Using mice deficient in the eosinophil granule products major basic protein (MBP) and eosinophil peroxidase (EPO), it was determined that eosinophils kill the larvae through an MBP-dependent mechanism in the primary immune response if other effector cells are absent. Infecting PHIL mice, which are eosinophil deficient, with S. stercoralis resulted in development of primary and secondary immune responses that were similar to those of wild-type mice, suggesting that eosinophils are not an absolute requirement for larval killing or development of secondary immunity. Treating PHIL mice with a neutrophil-depleting antibody resulted in a significant impairment in larval killing. Naïve and immunized mice with neutrophils deficient in myeloperoxidase (MPO) infected with S. stercoralis had significantly decreased larval killing. It was concluded that there is redundancy in the primary immune response, with eosinophils killing the larvae through an MBP-dependent mechanism and neutrophils killing the worms through an MPO-dependent mechanism. Eosinophils are not required for the development or function of secondary immunity, but MPO from neutrophils is required for protective secondary immunity.

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“…Eosinophils may also possess an immunoregulatory role in helminth infection [16]. Notably, eosinophils are able to present Strongyloides stercoralis-derived antigens in vitro and in mice in vivo [26,27], and to secrete Th2-related cytokines, e.g., IL-4 and IL-13, in murine Schistosoma mansoni infection [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…In systemic helminth infections, eosinophils may act as effector cells through killing of invading/migrating larvae in situ but also have an immunomodulatory role [16]. These distinct functions are mediated by various proteins that can be released from the granules, by receptors for, e.g., immunoglobulins and complement fragments, by the expression of various adhesion molecules, and by a range of cytokines and chemokines that can be secreted [17].…”

Section: Discussionmentioning

confidence: 99%

Hookworm-related cutaneous larva migrans in patients living in an endemic community in Brazil: Immunological patterns before and after ivermectin treatment

Shimogawara¹,

Hata²,

Schuster³

et al. 2013

European Journal of Microbiology and Immunology

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Hookworm-related cutaneous larva migrans (Hr-CLM) is caused by animal hookworm larvae migrating in the human epidermis where they elicit an inflammatory response. This study describes the immunological profile in Hr-CLM patients.In 77 Hr-CLM patients from Manaus, Brazil, peripheral eosinophils were counted, and serum concentrations of total immunoglobulin E (IgE) and selected cytokines were determined by ELISA before and after treatment with ivermectin. Controls included patients' household members (endemic controls), non-endemic Brazilian and Japanese individuals.Eosinophil counts and total IgE in Hr-CLM patients were higher than in controls and correlated with disease severity. Concentrations of interleukin (IL)-4, IL-5, IL-6, and IL-10 were higher in Hr-CLM patients than in endemic controls (p < 0.001) while no differences were detected for interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-1β, IL-2, or transforming growth factor (TGF)-β. Following ivermectin treatment, numbers of eosinophils and concentrations of IL-4, IL-5, and IL-10 decreased whereas IgE, IFN-γ, and TGF-β concentrations increased. The IL-5/IFN-γ ratio declined from 5.9 (interquartile range [IQR] 0.8-31.6) before to 0.1 (IQR 0.05-0.2; p = 0.001) after treatment.Thus, although an impact of other infections on the immune parameters determined cannot be excluded, Hr-CLM in endemic areas is associated with eosinophilia and elevated cytokine levels, particularly of IL-5 and IL-10, which decrease following ivermectin treatment.

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Granulocytes: effector cells or immunomodulators in the immune response to helminth infection?

Cited by 46 publications

References 200 publications

IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

Major Basic Protein from Eosinophils and Myeloperoxidase from Neutrophils Are Required for Protective Immunity to Strongyloides stercoralis in Mice

Hookworm-related cutaneous larva migrans in patients living in an endemic community in Brazil: Immunological patterns before and after ivermectin treatment

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