BACKGROUND: The lone star tick, Amblyomma americanum, is a three-host species widely distributed across North America and a vector for multiple human pathogens. Bites from this tick is also associated with alpha-gal syndrome, underscoring its growing public health importance. Adult female ticks undergo a prolonged feeding cycle divided into preparatory, slow-feeding, and rapid-feeding phases. Tick salivary glands are essential for successful blood feeding, producing a complex mixture of molecules that modulate host hemostasis, immunity, and tissue repair. The dynamic remodeling of the salivary gland transcriptome and proteome, termed the sialome switch, is thought to support prolonged feeding and immune evasion. To investigate the molecular mechanisms underlying the sialome switch, we performed high-throughput transcriptomic profiling of salivary glands from A. americanum adult females across the feeding cycle. RESULTS: Unlike previous studies that described the sialome switch in A. americanum by pooling ticks according to time post-attachment, we classified individuals based on average body weight, defining seven feeding stages encompassing unfed, slow-feeding, and rapid-feeding ticks. We identified 18,704 putative coding sequences (CDS) and revealed five distinct transcriptional profiles corresponding to different feeding stages. Unsupervised clustering indicated that most CDS were stage-specifically expressed, with temporal shifts observed in different protein families, including Kunitz-type, lipocalins, metalloproteases, and evasins. The transition from unfed to the slow-feeding phase corresponded to expression of a distinct subset of CDS within the signal transduction class, suggesting potential signaling pathways responsible for regulating this dynamic process. CONCLUSIONS: This study provides a high-resolution view of transcriptional dynamics in A. americanum salivary glands and identifies candidate molecular pathways regulating the sialome switch. These findings advance understanding of tick feeding biology and shed light on strategies ticks use to evade host defenses during prolonged blood meals.
Leishmaniasis is a vector-borne disease transmitted by female sand flies infected with Leishmania parasites. Cutaneous leishmaniasis is primarily caused by Leishmania major in the Old World and typically manifests as skin ulcers. The carbohydrate-rich molecules on the surface of Leishmania are crucial for the parasite's infectivity in the vertebrate host and vector. Among these, galactose moieties have been identified as promising targets for vaccines against leishmaniasis. This study investigates the potential of human monoclonal antibodies (mAbs) targeting α-Gal to prevent L major infection. Our results demonstrate that α-Gal-specific mAbs effectively bind to and agglutinate metacyclic and procyclic L major promastigotes. To assess the protective efficacy of these mAbs, we challenged α1,3-galactosyltransferase-deficient mice with L major. The mAb AG030 significantly delayed the onset of skin lesions and reduced the parasite burden. These findings provide proof of principle that α-Gal-targeting mAbs could serve as an intervention to prevent cutaneous leishmaniasis.
Owen A, Duong K, Symons J, Cross B, Ratchford A, et al.
Asia Pacific allergy •
Australia has the highest prevalence worldwide of tick-induced allergies (mammalian meat and tick allergy/anaphylaxis). Inappropriate tick removal techniques are known to trigger tick anaphylaxis. This study aimed to ascertain the evidence for the effectiveness of tick removal methods and their relationship to the outcomes of tick-induced allergies and tick-borne illnesses. The design involved is a systematic literature review. Scopus, Embase, and Medline were searched (September 20, 2023) for studies of tick removal techniques and for outcomes of tick-induced allergic reactions and tick-borne illnesses. Two reviewers reviewed abstracts and full texts. Included studies were appraised (Joanna Briggs Institute critical appraisal tools), and data were extracted, tabulated, and evaluated. Six studies investigated a relevant outcome, all of low or moderate quality. Tick-killing in situ before removal resulted in allergic reactions in only 3/61 patients and no anaphylaxis. 23/28 who presented to the Emergency Department following removal with tweezers had allergic reactions (one anaphylaxis). When those with known tick anaphylaxis killed ticks in situ before removal there was no subsequent anaphylactic reaction. A significant decrease in disease transmission and/or seropositivity ( and/or ) was shown with crushing ticks or gentle pressure before removal with fine-tipped forceps, forceps alone, and surgical tweezers. Manipulation before removal with tweezers made no difference to seropositivity. Few studies worldwide have examined outcomes of tick removal techniques. Tick-killing in situ reduces recurrent tick anaphylaxis in Australians. Early removal with forceps may be effective where tick-borne disease is of greater concern. Further studies of tick-killing in situ focusing upon disease transmission should be prioritized.
The journal of allergy and clinical immunology. In practice •
The severity of anaphylaxis is determined by many factors. The allergenic source as well as the age of the affected individual and the route of allergen exposure encompass the major contributors of the clinical outcome. Moreover, the severity can be modulated further by intrinsic and extrinsic factors. Among these, the genetic predisposition, certain comorbidities such as uncontrolled asthma, and hormonal fluctuations have been proposed as intrinsic and antihypertensive medications or physical activity as extrinsic factors. Recent advances have highlighted immunologic pathways that may exacerbate the response to allergens through receptors on mast cells, basophils, platelets, and other granulocytes. Atopy, platelet-activating factor acetylhydrolase deficiency, hereditary alpha tryptasemia, and clonal mast cell disorders are examples associated with genetic alterations that may predispose to severe anaphylaxis. Identifying risk factors that lower the threshold of reactivity or increase the severity of multisystem reactions is important in the management of this patient population.
Platts-Mills TAE, Commins SP, Biedermann T, van Hage M, Levin M, et al.
The Journal of allergy and clinical immunology •
The mammalian meat allergy known as the "α-Gal syndrome" relates to IgE specific for galactose-α-1,3-galactose (α-Gal), an oligosaccharide that is present in cells and tissues of nonprimate mammals. The recognition of delayed reactions to food derived from mammals in patients with IgE to α-Gal and also the association with tick bites have been increasing worldwide. In 2018, the National Institute of Allergy and Infectious Diseases, Division of Allergy, Immunology and Transplantation, sponsored a workshop on this emerging tick-related disease. International experts from the fields of tick biology, allergy, immunology, infectious disease, and dermatology discussed the current state of our understanding of this emerging medical condition. The participants provided suggestions for specific research priorities and for the development of resources to advance our knowledge of the mechanisms, diagnosis, management, and prevention of this allergic disease. This publication is a summary of the workshop and the panel's recommendations are presented herein.
The journal of allergy and clinical immunology. In practice •
Insect sting anaphylaxis and mast cell disorders are intertwined in a specific and unusual way. There may be specific subsets of clonal mast cell disorders that are predisposed to sting anaphylaxis. The clinical characteristics of the sting reactions should raise suspicion of underlying mastocytosis (eg, hypotension without hives especially in a male). A baseline serum tryptase level is helpful in the evaluation of patients with insect sting anaphylaxis because it correlates with important risks for these patients, and they have a high frequency of abnormally elevated baseline levels. Elevated baseline serum tryptase level has been reported to correlate with clonal mast cell disease in patients with insect sting anaphylaxis but may also indicate one of several possible underlying syndromes, including mast cell activation syndrome (MCAS), familial hypertryptasemia, and idiopathic anaphylaxis. There is some overlap in these conditions, so it is important to evaluate the clinical pattern at presentation as well as laboratory markers, and to consider bone marrow biopsy to make a final and specific diagnosis of clonal mast cell disease. The presence of venom-IgE does not prove that the patient's previous sting reactions were IgE-mediated, but even low levels of venom-IgE in patients with mastocytosis predispose to severe sting anaphylaxis. Evaluation of all these possible factors will affect the recommendation for venom immunotherapy.
Luke T, Bennett RS, Gerhardt DM, Burdette T, Postnikova E, et al.
The Journal of infectious diseases •
Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-α-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.
Carter MC, Ruiz-Esteves KN, Workman L, Lieberman P, Platts-Mills TAE, et al.
Allergy •
IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3-6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked.
Yilmaz B, Portugal S, Tran TM, Gozzelino R, Ramos S, et al.
Cell •
Glycosylation processes are under high natural selection pressure, presumably because these can modulate resistance to infection. Here, we asked whether inactivation of the UDP-galactose:β-galactoside-α1-3-galactosyltransferase (α1,3GT) gene, which ablated the expression of the Galα1-3Galβ1-4GlcNAc-R (α-gal) glycan and allowed for the production of anti-α-gal antibodies (Abs) in humans, confers protection against Plasmodium spp. infection, the causative agent of malaria and a major driving force in human evolution. We demonstrate that both Plasmodium spp. and the human gut pathobiont E. coli O86:B7 express α-gal and that anti-α-gal Abs are associated with protection against malaria transmission in humans as well as in α1,3GT-deficient mice, which produce protective anti-α-gal Abs when colonized by E. coli O86:B7. Anti-α-gal Abs target Plasmodium sporozoites for complement-mediated cytotoxicity in the skin, immediately after inoculation by Anopheles mosquitoes. Vaccination against α-gal confers sterile protection against malaria in mice, suggesting that a similar approach may reduce malaria transmission in humans.