Immune cells are highly dynamic in their response to the tissue environment. Most immune cells rapidly change their metabolic profile to obtain sufficient energy to engage in defensive or homeostatic processes. Such "immunometabolism" is governed through intermediate metabolites, and has a vital role in regulating immune-cell function. The underlying metabolic reactions are shaped by the abundance and accessibility of specific nutrients, as well as the overall metabolic status of the host. Here, we discuss how different immune-cell types gain a sufficient energy supply. We then explain how immune cells perform various functions under challenged conditions and expend energy to sustain homeostasis. Finally, we speculate on how the immune-cell metabolic profile might be modulated in health and disease, by manipulating nutrient availability. By such intervention, the recovery of patient with dysregulated immune system responses might be sped up and the fitness of an individual efficiently restored.

• Keywords
• energy demand, immune-cell polarization, immunometabolism, nutrient availability,
• MeSH
• Cell Differentiation MeSH
• Energy Metabolism * MeSH
• Immunity * MeSH
• Immune System MeSH
• Humans MeSH
• Metabolic Networks and Pathways MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Even though an association between inflammation and hypertension has been known for many years, it has not been simple to ascertain the role of several physiological responses involved. The innate immune response plays a critical role in these physiological responses. Innate immune cells can be activated directly by shear stress, activate the inflammasome and produce numerous cytokines and soluble mediators essential in hypertension. NFkB activation is mainly involved in the activation of innate immune cells. Shear stress also stimulates the expression of DAMP and PAMP receptors, enhancing pathogen and danger signals and magnifying inflammation. The adaptative immune response is activated with the increased antigen presentation resulting from the insults mentioned. Chronic inflammation may lead to autoimmunity. Peripheral hypoxia, a consequence of hypertension, activates hypoxia-inducing factors 1-α and 1-β (HIF-1α, HIF-1β), which modulate innate immune cells and promote inflammation. HIF-1α is involved in the upregulation of oxygen and nitrogen radical production proteins. HIF-1β down-regulates antioxidant enzymes. However, the critical evidence of the role of innate immune cells in hypertension came from the results of clinical trials involving therapies blocking inflammatory cytokines and Toll-like receptor expression. Several lines of research have been conducted on this complex disease. Pro-tolerogenic innate immune cells, myeloid suppressor cells, and M2 macrophages may play a crucial role in promoting or resolving inflammation, cardiovascular diseases and hypertension, and should be studied in detail.

• Keywords
• Sodium transport, antihypertensive therapy, hypertension, hypoxia, inflammasome, innate immune response, toll-like receptors,
• MeSH
• Cytokines metabolism   MeSH
• Hypertension * MeSH
• Hypoxia MeSH
• Humans MeSH
• Immunity, Innate * MeSH
• Inflammation metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines MeSH

The intracellular bacterial pathogen Francisella tularensis causes serious infectious disease in humans and animals. Moreover, F. tularensis, a highly infectious pathogen, poses a major concern for the public as a bacterium classified under Category A of bioterrorism agents. Unfortunately, research has so far failed to develop effective vaccines, due in part to the fact that the pathogenesis of intracellular bacteria is not fully understood and in part to gaps in our understanding of innate immune recognition processes leading to the induction of adaptive immune response. Recent evidence supports the concept that immune response to external stimuli in the form of bacteria is guided by the primary interaction of the bacterium with the host cell. Based on data from different Francisella models, we present here the basic paradigms of the emerging innate immune recognition concept. According to this concept, the type of cell and its receptor(s) that initially interact with the target constitute the first signaling window; the signals produced in the course of primary interaction of the target with a reacting cell act in a paracrine manner; and the innate immune recognition process as a whole consists in a series of signaling windows modulating adaptive immune response. Finally, the host, in the strict sense, is the interacting cell.

• Keywords
• Francisella tularensis, immune recognition, innate immunity, intracellular bacteria, signaling windows concept, spatiotemporal network,
• MeSH
• Adaptive Immunity MeSH
• Francisella tularensis immunology   MeSH
• Immune System MeSH
• Host-Pathogen Interactions immunology   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Paracrine Communication immunology   MeSH
• Immunity, Innate * MeSH
• Tularemia immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Days ago, the Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo "for their discovery of cancer therapy by inhibition of negative immune regulation". This news has increased the attention on immunotoxicity and immune evasion mechanisms, which are once again hot research topics. Actually, increasing lines of evidence show that trichothecene mycotoxins have a strong immunosuppressive effect. These mycotoxins suppress the host immunity and make them more sensitive to the infection of pathogens, including bacteria and viruses. However, the underlying mechanism(s) in this context is still poorly understood. Interestingly, recent work showed that an immune evasion mechanism might be involved in trichothecene immunotoxicity. In this work, we discuss the potential immune evasion mechanism in trichothecene immunotoxicity. More importantly, under these circumstances, we are pleased to compile a Special Issue entitled "Biochemistry, Molecular Biology, and Toxicology of Natural and Synthetic Toxins" for the International Journal of Molecular Sciences (IJMS). Researchers are encouraged to share their latest interesting findings with the readers of IJMS.

• Keywords
• T-2 toxin, immune evasion, immunotoxicity, negative immune regulations, trichothecenes,
• MeSH
• Immune Evasion * MeSH
• Immunosuppressive Agents pharmacology   therapeutic use   MeSH
• Humans MeSH
• Trichothecenes pharmacology   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Introductory Journal Article MeSH
• Editorial MeSH
• Names of Substances
• Immunosuppressive Agents MeSH
• Trichothecenes MeSH

In the temperate climates of central Europe and North America, two distinct honeybee (Apis mellifera) populations are found in colonies: short-living summer bees emerge in spring and survive until summer, whereas long-living winter bees emerge in late August and overwinter. Besides the difference in their life spans, each of these populations fulfils a different role in the colonies and individual bees have distinct physiological and immunological adaptations depending on their roles. For instance, winter worker bees have higher vitellogenin levels and larger reserves of nutrients in the fat body than summer bees. The differences between the immune systems of both populations are well described at the constitutive level; however, our knowledge of its inducibility is still very limited. In this study, we focus on the response of 10-day-old honeybee workers to immune challenges triggered in vivo by injecting heat-killed bacteria, with particular focus on honeybees that emerge and live under hive conditions. Responses to bacterial injections differed between summer and winter bees. Winter bees exhibited a more intense response, including higher expression of antimicrobial genes and antimicrobial activity, as well as a significant decrease in vitellogenin gene expression and its concentration in the hemolymph. The intense immune response observed in winter honeybees may contribute to our understanding of the relationships between colony fitness and infection with pathogens, as well as its association with successful overwintering.

• Keywords
• Antimicrobial peptides, Honeybee, Humoral immunity, Immune system, Longevity,
• MeSH
• Immunity * MeSH
• Seasons MeSH
• Bees MeSH
• Vitellogenins * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH
• North America MeSH
• Names of Substances
• Vitellogenins * MeSH

T-cell lymphomas (TCLs) are a rare and heterogeneous subgroup of non-Hodgkin lymphomas (NHLs), forming only 10 % of all NHL cases in Western countries. Resulting from their low incidence and heterogeneity, the current treatment outcome is generally unfavorable, with limited availability of novel therapeutic approaches. Therefore, the recent success of immune checkpoint inhibitors (ICIs) in cancer treatment motivated their clinical investigation in TCLs as well. Multiple studies showed promising results; however, cases of TCL hyperprogression following ICI treatment and secondary T-cell-derived malignancies associated with ICI treatment of other cancer types were also reported. In our review, we first briefly summarize classification of T-cell-derived malignancies, general anti-tumor immune response, immune evasion, and immune checkpoint signaling. Next, we provide an overview of immune checkpoint molecule deregulation in TCLs, summarize available studies of ICIs in TCLs, and review the above-mentioned safety concerns associa-ted with ICI treatment and T-cell-derived malignancies. Despite initial promising results, further studies are necessary to define the most suitable clinical applications and ICI therapeutic combinations with other novel treatment approaches within TCL treatment. ICIs, and their combinations, might hopefully bring the long awaited improvement for the treatment of T-cell-derived malignancies.

• Keywords
• ALCL, CTLA-4, ENKTL, LAG-3, MF, OX40/OX40L, PD-1, PD-L1, PTCL, SS, Sézary syndrome, T-cell lymphoma, T-cell-derived malignancies, TIGIT, TIM-3, anaplastic large cell lymphoma, anti-CTLA-4, anti-PD-1, anti-PD-L1, atezolizumab, avelumab, durvalumab, extranodal NK/T-cell lymphoma, geptanolimab, immune checkpoint inhibitors, immune checkpoints, ipilimumab, mycosis fungoides, nivolumab, pembrolizumab, peripheral T-cell lymphoma, sintilimab, toripalimab,
• MeSH
• Immune Checkpoint Inhibitors * therapeutic use   MeSH
• Humans MeSH
• Lymphoma, T-Cell * drug therapy   immunology   MeSH
• Immune Checkpoint Proteins metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Immune Checkpoint Inhibitors * MeSH
• Immune Checkpoint Proteins MeSH

Ticks are ectoparasitic arthropods that necessarily feed on the blood of their vertebrate hosts. The success of blood acquisition depends on the pharmacological properties of tick saliva, which is injected into the host during tick feeding. Saliva is also used as a vehicle by several types of pathogens to be transmitted to the host, making ticks versatile vectors of several diseases for humans and other animals. When a tick feeds on an infected host, the pathogen reaches the gut of the tick and must migrate to its salivary glands via hemolymph to be successfully transmitted to a subsequent host during the next stage of feeding. In addition, some pathogens can colonize the ovaries of the tick and be transovarially transmitted to progeny. The tick immune system, as well as the immune system of other invertebrates, is more rudimentary than the immune system of vertebrates, presenting only innate immune responses. Although simpler, the large number of tick species evidences the efficiency of their immune system. The factors of their immune system act in each tick organ that interacts with pathogens; therefore, these factors are potential targets for the development of new strategies for the control of ticks and tick-borne diseases. The objective of this review is to present the prevailing knowledge on the tick immune system and to discuss the challenges of studying tick immunity, especially regarding the gaps and interconnections. To this end, we use a comparative approach of the tick immune system with the immune system of other invertebrates, focusing on various components of humoral and cellular immunity, such as signaling pathways, antimicrobial peptides, redox metabolism, complement-like molecules and regulated cell death. In addition, the role of tick microbiota in vector competence is also discussed.

• Keywords
• cell-mediated immunity, immune signaling pathway, immune system, microbiota, tick-borne pathogen,
• MeSH
• Immunity, Cellular * MeSH
• Immunity, Humoral * MeSH
• Host-Parasite Interactions MeSH
• Ticks immunology   metabolism   MeSH
• Humans MeSH
• Tick-Borne Diseases immunology   metabolism   transmission   MeSH
• Salivary Glands immunology   metabolism   MeSH
• Saliva immunology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The history and evolutionary pathways of defense reactions among various forms of life are reconstructed. The vertebrates evolved step-by-step from their invertebrate ancestors living in the distant past. The ancestry of vertebrate defense mechanisms must be traceable to them because these functions cannot be considered separately from the common evolutionary schema. The first part of this survey is therefore devoted to the description of major defense reactions and achievements in invertebrates. Particular emphasis is given to the taxa of present-day invertebrates most likely to exhibit some relationship to the chordates and thus to show real traces of vertebrate immune patterns. The second part involves three key assemblages of deuterostomate animals--the echinoderms, the nonvertebrate chordates, and the first vertebrates because these animals are believed to have created the prerequisites for transition from the invertebrate type of defense to the vertebrate type of adaptive immunity.

• MeSH
• Biological Evolution * MeSH
• Arthropods immunology   MeSH
• Echinodermata immunology   MeSH
• Immunity * MeSH
• Immunocompetence MeSH
• Humans MeSH
• Mollusca immunology   MeSH
• Transplantation Immunology MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Tumor growth is controlled by natural antitumor immune responses alone or by augmented immune reactivity resulting from different forms of immunotherapy, which has demonstrated clinical benefit in numerous studies, although the overall percentage of patients with durable clinical responses remains limited. This is attributed to the heterogeneity of the disease, the inclusion of late-stage patients with no other treatment options and advanced tumor-associated immunosuppression, which may be consolidated by certain types of chemotherapy. Despite variable responsiveness to distinct types of immunotherapy, therapeutic cancer vaccination has shown meaningful efficacy for a variety of cancers. A key step during cancer vaccination involves the appropriate modeling of the functional state of dendritic cells (DCs) capable of co-delivering four critical signals for proper instruction of tumor antigen-specific T cells. However, the education of DCs, either directly in situ, or ex vivo by various complex procedures, lacks standardization. Also, it is questioned whether ex vivo-prepared DC vaccines are superior to in situ-administered adjuvant-guided vaccines, although both approaches have shown success. Evaluation of these variables is further complicated by a lack of consensus in evaluating vaccination clinical study end points. We discuss the role of signals needed for the preparation of classic in situ and modern ex vivo DC vaccines capable of proper reprogramming of antitumor immune responses in patients with cancer.

• Keywords
• costimulation, homing signal, immune adjuvants, polarizing signal, therapeutic cancer vaccines,
• MeSH
• Adjuvants, Immunologic therapeutic use   MeSH
• Antigens, Neoplasm immunology   MeSH
• Dendritic Cells immunology   MeSH
• Immune Tolerance immunology   MeSH
• Immunotherapy * MeSH
• Humans MeSH
• Neoplasms immunology   pathology   therapy   MeSH
• Immunity, Innate drug effects   MeSH
• Cancer Vaccines therapeutic use   MeSH
• T-Lymphocytes immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• Antigens, Neoplasm MeSH
• Cancer Vaccines MeSH

Introduction: The expiry of patents for biologics has led to the introduction of biosimilars for the treatment of immune-mediated inflammatory diseases (IMIDs). These treatment alternatives may allow earlier and wider access to appropriate therapy for patients without increasing the economic burden on health-care systems. Prescription of biosimilars to treatment-naïve patients is well accepted; however, additional considerations must be taken into account when switching clinically stable patients from reference products to biosimilars. Area covered: We discuss the current considerations related to switching from reference products to biosimilars from a physician and patient perspective. We review the clinical data and real-life experience on switching patients with IMIDs, present the position of the relevant medical societies, and discuss the importance of patient-physician communication and need for shared decision-making. Expert opinion: The introduction of biosimilars provides an opportunity to expand access to treatment for patients with IMIDs across Europe and support the financial sustainability of health-care systems. We anticipate that as the real-world evidence base grows, confirming the results of clinical trials, there will be a corresponding increase in physician and patient acceptance, not only to initiating treatment with a biosimilar, but also to switching medication from a reference product to a biosimilar.

• Keywords
• Biological therapy, biosimilar, immune-mediated inflammatory disease, switching,
• MeSH
• Biosimilar Pharmaceuticals therapeutic use   MeSH
• Humans MeSH
• Immune System Diseases drug therapy   genetics   immunology   MeSH
• Randomized Controlled Trials as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Biosimilar Pharmaceuticals MeSH