Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion

Chen, Fei; Wu, Wenhui; Millman, Ariel; Craft, Joshua; Chen, Eunice; Patel, Nirav; Boucher, Jean Luc; Urban, Joseph F.; Kim, Charles C.; Gause, William C.

doi:10.1038/ni.2984

Cited by 308 publications

(411 citation statements)

References 54 publications

Supporting

Mentioning

387

Contrasting

Unclassified

Order By: Relevance

“…Eotaxin-1/CCL11 promotes chemotaxis of eosinophils, which produce IL-4 and contribute to the induction of Th2 immune responses. Conversely, KC/CXCL1 promotes chemotaxis of neutrophils, which produce IL-13 and contribute to the induction of Th2 immune responses in the Nb infection model (31). The expression levels of Eotaxin-1/CCL11 and KC/CXCL1 in the lung were not significantly changed in steady state by depletion of NK cells (Fig.…”

Section: Resultsmentioning

confidence: 95%

“…Therefore, we investigated the effect of depletion of NK cells on gene expressions in the lung where Th2 immune responses were induced by Nb and found a significant increase of the expression of Eotaxin-1/CCL11 and KC/CXCL1 in the lung by depletion of NK cells, suggesting that NK cells might regulate migration of eosinophils and neutrophils. Eosinophils are well known to contribute to the induction of Th2 immune responses, and neutrophils also contribute to the induction of Th2 immune responses in the Nb infection model (31). Considering these results and the strong capacity of IL4-NK cells to produce cytokines, the roles of IL4-NK-like cells in the Nb infection model might keep the balance of Th1/Th2 immune responses.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics

Kiniwa

Enomoto

Terazawa

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Natural killer (NK) cells are known to be activated by Th1-type cytokines, such as IL-2, -12, or -18, and they secrete a large amount of IFN-γ that accelerates Th1-type responses. However, the roles of NK cells in Th2-type responses have remained unclear. Because IL-4 acts as an initiator of Th2-type responses, we examined the characteristics of NK cells in mice overexpressing IL-4. In this study, we report that IL-4 overexpression induces distinctive characteristics of NK cells (B220 high /CD11b low /IL-18Rα low ), which are different from mature conventional NK (cNK) cells (B220 low /CD11b high /IL-18Rα high ). IL-4 overexpression induces proliferation of tissue-resident macrophages, which contributes to NK cell proliferation via production of IL-15. These IL-4-induced NK cells (IL4-NK cells) produce higher levels of IFN-γ, IL-10, and GM-CSF, and exhibit high cytotoxicity compared with cNK cells.

show abstract

Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics

Kiniwa

Enomoto

Terazawa

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Neutrophils have been associated with lung haemorrhagic foci in Nb-infected mice 12,17 and recently have been shown to be important for the priming of an anamnestic protective immune response against Nb 18 . Furthermore, neutrophildependent extracellular traps have been shown to compromise Strongyloides venezuelensis larval migration in skin 19 .…”

Section: Resultsmentioning

confidence: 99%

ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms

et al. 2015

View full text Add to dashboard Cite

Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4 þ T cells and Group 2 innate lymphoid cells (ILC2s) work in concert to block Nippostrongylus brasiliensis (Nb) development in the parenchyma within 48 h in mice. Immune-damaged larvae have a striking morphological defect that is dependent on the expansion of IL-13-producing ILC2 and CD4 þ T cells, and the activation of M2 macrophages. This T-cell requirement can be bypassed by administration of IL-2 or IL-33, resulting in expansion of IL-13-producing ILC2s and larval killing. Depletion of ILC2s inhibits larval killing in IL-2-treated mice. Our results broaden understanding of ILC2's role in immunity to helminths by demonstrating that they not only act as alarmin sensors, but can also be sustained by CD4 þ T cells, ensuring both the prompt activation and the maintenance of IL-13-dependent M2 macrophage immunity in the lung.

show abstract

Section: Tumor-induced Neutrophil Polarization and Activationmentioning

confidence: 99%

“…IL-4 and IL-13) or whether neutrophils produce these cytokines to affect disease phenotype. Although some studies addressing these issues are emerging 94,95 , the lack of concrete evidence in mice or humans raises the question of whether the N1/N2 terminology can be applied to cancerassociated neutrophils.The study proposing the N1/N2 terminology characterized N1 neutrophils by a hypersegmented nucleus and N2 neutrophils by banded or ring-like nuclei 65 . Because nuclear morphology is a hallmark of neutrophil differentiation 10 , it is unclear whether the socalled N2 neutrophils are just immature cells or represent a distinct polarized state, leaving the relationship between polarization and maturation unresolved.…”

mentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

View full text Add to dashboard Cite

SummaryNeutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view.The traditionally held belief that neutrophils are inert bystanders is being challenged by recent literature. Emerging evidence indicates that tumors manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumor behavior. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets. 2The name neutrophil -given to polymorphonuclear, granulocytic cells by Paul Ehrlich in the late 19th century -is based on the inability of these cells to retain acidic or basic dyes and for their preferential uptake of pH neutral dyes 1 . Although their neutral staining led to the identification of these cells, neutrophils in the cancer setting are anything but neutral.Neutrophils in tumor-bearing hosts can oppose or potentiate cancer progression. These two types of behavior are controlled by signals emanating from cancer cells or stromal cells within the tumor microenvironment, which educate neutrophils to execute the demise of the tumor or facilitate support networks that lead to its expansive spread. These functions can occur locally in or around the tumor microenvironment, as well as systemically in distant organs.Until the past few years, other immune cells such as macrophages have overshadowed the role of neutrophils in cancer. But recent studies and the development of new genetic tools have provided the cancer community with new insights into the profound influence of these dynamic cells by uncovering distinct capabilities for neutrophils throughout each step of carcinogenesis: from tumor initiation to primary tumor growth to metastasis.During these processes, neutrophils take on different phenotypes and sometimes opposing functions. Emerging evidence also indicates that these cells are highly influential, and are able to change the behavior of other tumor-associated cell types -primarily other immune cells. In this Review, we focus on how tumors manipulate the generation and release of neutrophils from the bone marrow. We discuss the mechanisms identified in animal models by which neutrophils participate in tumor initiation, growth and metastasis. Finally, we highlight the potential of these cells as clinical biomarkers and therapeutic targets. In humans, neutrophils are the most abundant immune cell population, representing 50-70% of all leukocytes. Over 10 11 neutrophils may be produced per day 2 , and tumors can increase this number by even more. Indeed, patients with various cancer types, including but not limited to breast, lung and colorectal cancer, often exhibit increased numbers of circulating neutrophils 3,4 . Recent studies have identified key pathways that tumors exploit to disrupt normal neutrophil homeostasis and these are discuss...

show abstract

Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion

Cited by 308 publications

References 54 publications

NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics

NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics

ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms

Neutrophils in cancer: neutral no more

Contact Info

Product

Resources

About