-
Frontiers in Immunology 2022Basophils have been implicated in type 2 inflammation and numerous disorders in the skin such as helminth infection, atopic dermatitis, and urticaria. Although similar...
Basophils have been implicated in type 2 inflammation and numerous disorders in the skin such as helminth infection, atopic dermatitis, and urticaria. Although similar in form and function to tissue-resident mast cells, classical studies on basophils have centered on those from the hematopoietic compartment. However, increasing studies in tissues like the skin demonstrate that basophils may take on particular characteristics by responding to unique developmental, chemotactic, and activation cues. Herein, we highlight how recent studies in barrier immunology suggest the presence of skin-homing basophils that harbor a unique identity in terms of phenotype, function, and motility. These concepts may uniquely inform how basophils contribute to diseases at multiple epithelial surfaces and our ability to therapeutically target the innate immune system in disease.
Topics: Humans; Basophils; Skin; Urticaria; Dermatitis, Atopic; Inflammation
PubMed: 36618424
DOI: 10.3389/fimmu.2022.1059098 -
Frontiers in Immunology 2020Helminths remain one of the most prolific pathogens in the world. Following infection helminths interact with various epithelial cell surfaces, including skin, lung, and... (Review)
Review
Helminths remain one of the most prolific pathogens in the world. Following infection helminths interact with various epithelial cell surfaces, including skin, lung, and gut. Recent works have shown that epithelial cells produce a series of cytokines such as TSLP, IL-33, and IL-25 that lead to the induction of innate and acquired type 2 immune responses, which we named Type 2 epithelial cytokines. Although basophils and eosinophils are relatively rare granulocytes under normal conditions (0.5% and 5% in peripheral blood, respectively), both are found with increased frequency in type 2 immunity, including allergy and helminth infections. Recent reports showed that basophils and eosinophils not only express effector functions in type 2 immune reactions, but also manipulate the response toward helminths. Furthermore, basophils and eosinophils play non-redundant roles in distinct responses against various nematodes, providing the potential to intervene at different stages of nematode infection. These findings would be helpful to establish vaccination or therapeutic drugs against nematode infections.
Topics: Animals; Basophils; Eosinophils; Helminths; Humans; Immunity; Nematode Infections
PubMed: 33335529
DOI: 10.3389/fimmu.2020.583824 -
The Journal of Allergy and Clinical... Oct 2013Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their... (Review)
Review
Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their phenotypic similarities with mast cells resulted in this cell lineage being historically overlooked, both clinically and experimentally. However, recent studies in human subjects and murine systems have shown that basophils perform nonredundant effector functions and significantly contribute to the development and progression of TH2 cytokine-mediated inflammation. Although the potential functions of murine and human basophils have provoked some controversy, recent genetic approaches indicate that basophils can migrate into lymphoid tissues and, in some circumstances, cooperate with other immune cells to promote optimal TH2 cytokine responses in vivo. This article provides a brief historical perspective on basophil-related research and discusses recent studies that have identified previously unappreciated molecules and pathways that regulate basophil development, activation, and function in the context of allergic inflammation. Furthermore, we highlight the unique effector functions of basophils and discuss their contributions to the development and pathogenesis of allergic inflammation in human disease. Finally, we discuss the therapeutic potential of targeting basophils in preventing or alleviating the development and progression of allergic inflammation.
Topics: Animals; Basophils; Cytokines; Humans; Hypersensitivity, Immediate; Inflammation; Mice; Th2 Cells
PubMed: 24075190
DOI: 10.1016/j.jaci.2013.07.046 -
Allergology International : Official... Apr 2016Basophils and mast cells play important roles in host defense against parasitic infections and allergic responses. Several progenitor populations, either shared or... (Review)
Review
Basophils and mast cells play important roles in host defense against parasitic infections and allergic responses. Several progenitor populations, either shared or specific, for basophils and/or mast cells have been identified, thus elucidating the developmental pathways of these cells. Multiple transcription factors essential for their development and the relationships between them have been also revealed. For example, IRF8 induces GATA2 expression to promote the generation of both basophils and mast cells. The STAT5-GATA2 axis induces C/EBPα and MITF expression, facilitating the differentiation into basophils and mast cells, respectively. In addition, C/EBPα and MITF mutually suppress each other's expression. This review provides an overview of recent advances in our understanding of how transcription factors regulate the development of basophils and mast cells.
Topics: Animals; Basophils; Binding Sites; Cell Differentiation; Gene Expression Regulation, Developmental; Hematopoiesis; Hematopoietic Stem Cells; Humans; Mast Cells; Mice; Mice, Knockout; Models, Animal; Protein Binding; Transcription Factors
PubMed: 26972050
DOI: 10.1016/j.alit.2016.01.006 -
Frontiers in Immunology 2022Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an... (Review)
Review
Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an anti-human IgE antibody that traps IgE and prevents its binding to high-affinity IgE receptors, is effective in treating urticaria. We recently experienced a case of urticaria refractory to antihistamine therapy in which the peripheral-blood basophil count responded to omalizumab therapy and its withdrawal. Furthermore, the peripheral-blood basophils showed an unexpected increase in the expression of a cell surface activation marker. This phenomenon has been reported by other analyses of basophil and mast cell dynamics during omalizumab treatment. Here, we analyze these observations and formulate a hypothesis for the role of basophils in urticaria. Specifically, that activated basophils migrate to the local skin area, lowering peripheral-blood counts, omalizumab therapy alters basophilic activity and causes their stay in the peripheral blood. We hope that our analysis will focus urticaria research on basophils and reveal new aspects of its pathogenesis.
Topics: Anti-Allergic Agents; Basophils; Humans; Immunoglobulin E; Omalizumab; Urticaria
PubMed: 35663949
DOI: 10.3389/fimmu.2022.883692 -
Current Allergy and Asthma Reports Nov 2018The basophil activation test (BAT) using flow cytometry has supplanted traditional methods of measuring basophil degranulation using histamine and other mediator... (Review)
Review
PURPOSE OF REVIEW
The basophil activation test (BAT) using flow cytometry has supplanted traditional methods of measuring basophil degranulation using histamine and other mediator release, and can be used for clinical applications as well as to explore the immune mechanisms of effector cell response to allergen. This review discusses the advancements made in clinical, diagnostic and laboratory research of allergy utilizing an ever-evolving BAT.
RECENT FINDINGS
Being an in vitro surrogate of the allergic reaction that happens in vivo in the sick patient, the BAT can be used to support the diagnosis of various allergic conditions, such as food, drug, respiratory and insect venom allergies, and the assessment of clinical response to allergen-specific immunotherapy and other immunomodulatory treatments. The BAT can also be used for research purposes to explore the mechanisms of allergy and tolerance at the level of the basophil, for instance by manipulating IgE and IgG and their receptors and by studying intracellular signalling cascade in response to allergen. This review covers the applications of the BAT to the clinical management of allergic patients and the increased understanding of the mechanisms of immune response to allergens as well as technological advancements made in recent years.
Topics: Basophils; Cell Degranulation; Humans; Hypersensitivity; Immunomodulation
PubMed: 30430289
DOI: 10.1007/s11882-018-0831-5 -
Urologic Oncology Jun 2022Biomarkers have the potential to provide clinical guidance, but there is limited data for biomarkers in metastatic hormone sensitive prostate cancer (mHSPC).
BACKGROUND
Biomarkers have the potential to provide clinical guidance, but there is limited data for biomarkers in metastatic hormone sensitive prostate cancer (mHSPC).
METHODS
We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014-2020) in the United States of America (USA). We collected demographics, disease characteristics, and laboratory data, including complete blood counts (CBC) at the start of upfront therapy. We evaluated overall survival (OS) and progression-free survival (PFS) associated with baseline lab values.
RESULTS
165 patients were included with a median follow-up time of 33.5 months (mo). 105 (63.6%) had Gleason scores of 8-10 and 108 (65.9%) were classified as high-volume disease. 92 patients received upfront docetaxel (55.8%) and 73 received upfront abiraterone (44.2%). Univariate analyses (UVA) and multivariable analyses (MVA) identified worse clinical outcomes (CO) associated with elevated basophils and basophil-to-lymphocyte ratio (BLR). Based on MVA, elevated basophils (defined as ≥0.1, optimal cut) were associated with a hazard ratio (HR) of 3.51 (95% CI 1.65-7.43, P 0.001) for OS and HR of 1.88 (95% CI 1.05-3.38, P 0.034) for PFS. Our MVA also found that BLR ≥0.0142 was associated with HR 2.11 (95% CI 1.09-4.10, P 0.028) for OS; however, PFS was not statistically significant.
CONCLUSION
We conclude that elevated baseline basophils and BLR are associated with worse clinical outcomes in mHSPC. Although results require further validation, BLR is a potential prognostic biomarker.
Topics: Basophils; Docetaxel; Hormones; Humans; Lymphocytes; Male; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies
PubMed: 35466038
DOI: 10.1016/j.urolonc.2022.03.016 -
Frontiers in Immunology 2020Ticks are blood-sucking arthropods of great importance in the medical and veterinary fields worldwide. They are considered second only to mosquitos as vectors of... (Review)
Review
Ticks are blood-sucking arthropods of great importance in the medical and veterinary fields worldwide. They are considered second only to mosquitos as vectors of pathogenic microorganisms that can cause serious infectious disorders, such as Lyme borreliosis and tick-borne encephalitis. Hard () ticks feed on host animals for several days and inject saliva together with pathogens to hosts during blood feeding. Some animal species can acquire resistance to blood-feeding by ticks after a single or repeated tick infestation, resulting in decreased weights and numbers of engorged ticks or the death of ticks in subsequent infestations. Importantly, this acquired tick resistance (ATR) can reduce the risk of pathogen transmission from pathogen-infected ticks to hosts. This is the basis for the development of tick antigen-targeted vaccines to forestall tick infestation and tick-borne diseases. Accumulation of basophils is detected in the tick re-infested skin lesion of animals showing ATR, and the ablation of basophils abolishes ATR in mice and guinea pigs, illustrating the critical role for basophils in the expression of ATR. In this review article, we provide a comprehensive overview of recent advances in our understanding of the cellular and molecular mechanisms responsible for the development and manifestation of ATR, with a particular focus on the role of basophils.
Topics: Animals; Basophils; Histamine; Histamine Release; Host-Pathogen Interactions; Humans; Immunoglobulin E; Immunologic Memory; Insect Bites and Stings; Saliva; Skin; Tick-Borne Diseases; Ticks; Vaccination; Vaccines
PubMed: 33154758
DOI: 10.3389/fimmu.2020.601504 -
Current Opinion in Allergy and Clinical... Oct 2021Utilization of basophil activation in the diagnosis and monitoring of food allergy has gained increasing recognition. An ex-vivo functional assay, basophil activation... (Review)
Review
PURPOSE OF REVIEW
Utilization of basophil activation in the diagnosis and monitoring of food allergy has gained increasing recognition. An ex-vivo functional assay, basophil activation reflects clinical reactivity, thereby providing clinically relevant insights. Moreover, as a biomarker of reactivity and tolerance, basophil activation testing (BAT) may provide a useful tool for management of food allergies. Despite its utility, significant limitations of BAT have prevented widespread use. Addressing these limitations will increase the future application and adoption of BAT in food allergy.
RECENT FINDINGS
A number of clinical trials in the past few years have demonstrated the use of BAT in the diagnosis and treatment of food allergy. Specifically, BAT has been found to be a biomarker of tolerance.
SUMMARY
Basophil activation testing is an effective biomarker for diagnosis and monitoring of food allergy.
Topics: Allergens; Basophils; Biomarkers; Food Hypersensitivity; Humans; Immune Tolerance
PubMed: 34374669
DOI: 10.1097/ACI.0000000000000774 -
Frontiers in Immunology 2020Basophils were identified in human peripheral blood by Paul Ehrlich over 140 years ago. Human basophils represent <1% of peripheral blood leukocytes. During the last... (Review)
Review
Basophils were identified in human peripheral blood by Paul Ehrlich over 140 years ago. Human basophils represent <1% of peripheral blood leukocytes. During the last decades, basophils have been described also in mice, guinea pigs, rabbits, and monkeys. There are many similarities, but also several immunological differences between human and mouse basophils. There are currently several strains of mice with profound constitutive or inducible basophil deficiency useful to prove that these cells have specific roles . However, none of these mice are solely and completely devoid of all basophils. Therefore, the relevance of these findings to humans remains to be established. It has been known for some time that basophils have the propensity to migrate into the site of inflammation. Recent observations indicate that tissue resident basophils contribute to lung development and locally promote M2 polarization of macrophages. Moreover, there is increasing evidence that lung-resident basophils exhibit a specific phenotype, different from circulating basophils. Activated human and mouse basophils synthesize restricted and distinct profiles of cytokines. Human basophils produce several canonical (e.g., VEGFs, angiopoietin 1) and non-canonical (i.e., cysteinyl leukotriene C) angiogenic factors. Activated human and mouse basophils release extracellular DNA traps that may have multiple effects in cancer. Hyperresponsiveness of basophils has been demonstrated in patients with JAK2-positive polycythemia vera. Basophils are present in the immune landscape of human lung adenocarcinoma and pancreatic cancer and can promote inflammation-driven skin tumor growth. The few studies conducted thus far using different models of basophil-deficient mice have provided informative results on the roles of these cells in tumorigenesis. Much more remains to be discovered before we unravel the hitherto mysterious roles of basophils in human and experimental cancers.
Topics: Angiogenesis Inducing Agents; Animals; Basophils; Carcinogenesis; Humans; Macrophages; Neoplasms
PubMed: 33013885
DOI: 10.3389/fimmu.2020.02103