editorial neutrophils: their role in innate and adaptive ... · neutrophils display an array of...

EditorialNeutrophils: Their Role in Innate and Adaptive Immunity 2017

Carlos Rosales,1 Clifford A. Lowell,2 Michael Schnoor,3 and Eileen Uribe-Querol4

1Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510 Ciudad de México, Mexico2Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA3Department of Molecular Biomedicine, CINVESTAV-IPN, 07360 Ciudad de México, Mexico4Facultad de Odontología, Universidad Nacional Autónoma de México, 04510 Ciudad de México, Mexico

Correspondence should be addressed to Carlos Rosales; [email protected]

Received 13 June 2017; Accepted 13 June 2017; Published 7 November 2017

Copyright © 2017 Carlos Rosales et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Neutrophils have long been regarded as the first line ofdefense against infection and one of the main cell typesinvolved in initiation of the inflammatory response. It is gen-erally accepted that the innate immunity functions of neutro-phils are mainly mediated by phagocytosis, release ofgranules, and formation of neutrophil extracellular traps(NETs). In recent years, however, accumulating evidencehas shown that neutrophils possess greater functional diver-sity than previously appreciated. Thus, the classical view ofneutrophils as simple cytotoxic leukocytes against pathogensis currently being revisited. Neutrophils display an array ofbiological functions important for both innate and adaptiveimmune responses. Neutrophils can produce many cytokinesand chemokines upon stimulation, and in this way, they caninteract with endothelial cells, dendritic cells, macrophages,natural killer cells, T lymphocytes, and B lymphocytes.Through all these interactions, neutrophils can either activateor downregulate both innate and adaptive immunity. Thenovel functions of neutrophils reveal that these cells haveunanticipated roles in homeostasis, as well as in severaldiseases such as atherosclerosis, stroke, chronic obstructivepulmonary diseases, and cancer.

To continue elucidating the complex role of neutrophilsin infection, inflammation, and immunity, this secondspecial issue has brought together original and review articlesthat will help us to better understand the complex and fasci-nating neutrophil biology.

As mentioned before, the primary role of neutrophils isthe clearance of extracellular pathogens, through phagocyto-sis, release of a broad array of effector molecules, and the

production of extracellular traps. However, some pathogenshave also the capacity to overcome neutrophil-mediated hostdefense mechanisms and establish infections leading todisease. One such pathogen is the bacteria Staphylococcusaureus, which can block chemotaxis and phagocytosis, thusevading killing by neutrophils. In addition, S. aureus cansurvive within neutrophils and promote neutrophil cytolysis,causing the release of molecules that promote local inflam-mation. The article by T.-S. Teng and colleagues describesthe mechanisms by which neutrophils kill extracellularpathogens and how pathogens evade neutrophil defensemechanisms. They also discuss ideas that might be usefulfor the development of novel therapies against infectionscaused by antibiotic-resistant pathogens.

Similarly, the role of NETs is primarily to entrap extracel-lular microbes and, in this way, to keep an early infectionlocalized. Yet, besides microorganisms, other stimuli can alsoactivate neutrophils to produce NETs. The article by B. Radasummarizes the recently described ability of differentmicrocrystals to induce NET formation. Microcrystals areinsoluble crystals with a size of 1–100 micrometers thatcan irritate phagocytes including neutrophils and typicallytrigger an inflammatory response. The effect on neutro-phils by microcrystals in adjuvant and by microcrystalsassociated with diseases such as gout, atherosclerosis, andsilicosis is discussed.

Neutrophils play an essential role during an inflamma-tory response. They are rapidly mobilized from the circula-tion into damaged tissues. The blood supply of neutrophilsis at the same time replenished by a rapid recruitment of

HindawiJournal of Immunology ResearchVolume 2017, Article ID 9748345, 2 pageshttps://doi.org/10.1155/2017/9748345

https://doi.org/10.1155/2017/9748345

neutrophils from the bone marrow to the vasculature. A greatdeal is known about the mechanism for neutrophil migrationinto tissues. However, there is very little information aboutthe molecular signals that regulate the entry of neutrophilsinto the circulation. In an attempt to learn more about thisprocess, the article by C. Zuñiga-Traslaviña and colleaguesdescribes a zebrafish model, to assess the role of CXC-chemokines and CXC-receptor 2, in neutrophil migrationinto the blood circulation after injury. They found that theCXCL8b/CXCR2 axis is an important regulator of neutrophilentry into the bloodstream. On the other hand, when neutro-phils arrive at sites of inflammation, they release variouscytokines. The signaling machinery required for productionof inflammatory and immunomodulatory cytokines and forextending the life of neutrophils at inflamed sites is poorlyknown. Thus, this is another area of intense study in theneutrophil field. The article by T. Ear and colleagues tells usabout the constitutive expression of various Src family kinaseisoforms and of spleen tyrosine kinase (Syk) in neutrophilsand how the inhibition of these tyrosine kinases selectivelyblocks inflammatory cytokine production by acting posttran-scriptionally. In contrast, delayed apoptosis seems to beindependent of these kinases. These findings have implica-tions for the future identification of potential moleculartargets that could be useful in therapeutic intervention ofchronic inflammatory conditions.

The involvement of neutrophils in several inflammatorypathologies is being recognized more and more, with thegrowing understanding of the proinflammatory and immu-nomodulatory properties of these cells. In some conditions,such as stroke and cancer, the numbers of immune cellscan significantly predict the clinical outcome of the disease.In particular, the neutrophil-to-lymphocyte ratio was shownto predict hemorrhagic transformation and the clinicaloutcome of stroke. However, the immunological mecha-nisms underlying these effects are poorly understood. In thearticle by J. Ruhnau and colleagues, the role of neutrophilsin brain ischemia is discussed. Neutrophils are the first cellsto invade injured tissue after focal brain ischemia. In theseconditions, they can enhance tissue damage and even pro-mote more ischemic injury by inducing thrombus formation.Yet, neutrophils are also beneficial because they are involvedin triggering the removal of cell debris and are essential fordefense against bacterial infections. Thus, therapeutic inter-ventions that target neutrophils to prevent stroke shouldpreserve their functions outside the central nervous system.

In other pathologies, neutrophils also play an essentialrole. For example, respiratory diseases such as asthma andchronic obstructive pulmonary disease (COPD) are charac-terized by an excessive infiltration of neutrophils. It isgenerally accepted that subsequent activation of these neu-trophils promotes production of reactive oxygen speciesand release of proteases resulting in tissue damage andalveolar airspace enlargement. The article by J. Liu andcolleagues reviews the role of neutrophils in respiratorydiseases, describing recent studies on mechanisms for neu-trophil trafficking, activation, and cell death. The studies onneutrophil function with isolated cells do not provide acomplete picture because cells are taken from the

inflammatory environment of the disease. Animal modelsplay an important role in studying the underlying mecha-nisms of respiratory diseases such as COPD as they addressquestions involving integrated whole body responses. Thearticle by G. Huang and colleagues presents a review of thecurrent animalmodels of COPD, focusing on their advantagesand disadvantages on immune responses and neutrophilicinflammation. Finally, the article by C. K. Mårdh andcolleagues discusses novel therapeutic approaches for respira-tory diseases that target neutrophil function. They describehow targeting the chemokine receptors CXCR2 and CXCR1could be regulated during neutrophil trafficking and howtargeting the enzyme PI3K could modulate neutrophil func-tion. Also, they explain how protease inhibitors that targetmatrix metalloproteinases and neutrophil serine proteasescould prevent excessive tissue damage.

Together, these articles provide a sample of the multipleand complex functions of neutrophils for fighting infectionsand for controlling immunity. They also underline therelevant role of neutrophils in pathological conditions andprovide guidance for future research on the cell biology ofthese fascinating leukocytes.

Carlos RosalesClifford A. LowellMichael Schnoor

Eileen Uribe-Querol

2 Journal of Immunology Research

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