Cells In Infection Research Articles

Role of Dendritic Cells in Viral Brain Infections.

To gain access to the brain, a so-called immune-privileged organ due to its physical separation from the blood stream, pathogens and particularly viruses have been selected throughout evolution for their use of specific mechanisms. They can enter the central nervous system through direct infection of nerves or cerebral barriers or through cell-mediated transport. Indeed, peripheral lymphoid and myeloid immune cells can interact with the blood–brain and the blood–cerebrospinal fluid barriers and allow viral brain access using the “Trojan horse” mechanism. Among immune cells, at the frontier between innate and adaptive immune responses, dendritic cells (DCs) can be pathogen carriers, regulate or exacerbate antiviral responses and neuroinflammation, and therefore be involved in viral transmission and spread. In this review, we highlight an important contribution of DCs in the development and the consequences of viral brain infections.

Regulation of T Helper and Regulatory T Cells by Lactobacillus Plantarum IS-10506 Supplementation to Human Immunodeficiency Virus-Infected Children Under Antiretroviral Therapy

Human immunodeficiency virus infection is associated with impairment of T helper 1, T helper 2, regulatory T, and T helper Type 17 homeostasis. While probiotics are widely known to improve these changes, understanding of their role on children’s immune system remains limited. In a randomized, double-blind, and placebo-controlled study conducted in Dr. Soetomo General Hospital, Surabaya from December 2012 to March 2013, we have investigated the effect of Lactobacillus plantarum IS-10506 on the regulation of T helper and regulatory T cell in children infected with human immunodeficiency virus receiving antiretroviral therapy for at least 6 months. Twenty-one human immunodeficiency virus infected children were divided into placebo and probiotic groups and L. plantarum IS-10506 was administered at a dose of 2.86 × 1010 colony forming units/day for 6 weeks. Levels of interferon-γ, interleukin-4, transforming growth factor-β, and interleukin-17 were analyzed before and after treatment as an indicator of T-cell regulation of T helper and regulatory T cells. The results show a significant increase in transforming growth factor-β level ( p = 0.003) after administration of L. plantarum IS-10506 compared to placebo with the first-line antiretroviral therapy group. There was no reported adverse effect in this study. In conclusion, L. plantarum IS-10506 increases the regulation of regulatory T cell in human immunodeficiency virus infection in children receiving first-line antiretroviral therapy treatment.

Human placental hematopoietic stem cell derived natural killer cells (CYNK-001) mediate protection against influenza a viral infection

ABSTRACT Influenza A virus (IAV) infections are associated with a high healthcare burden around the world and there is an urgent need to develop more effective therapies. Natural killer (NK) cells have been shown to play a pivotal role in reducing IAV-induced pulmonary infections in preclinical models; however, little is known about the therapeutic potential of adoptively transferred NK cells for IAV infections. Here, we investigated the effects of CYNK-001, human placental hematopoietic stem cell derived NK cells that exhibited strong cytolytic activity against a range of malignant cells and expressed high levels of activating receptors, against IAV infections. In a severe IAV-induced acute lung injury model, mice treated with CYNK-001 showed a milder body weight loss and clinical symptoms, which led to a delayed onset of mortality, thus demonstrating their antiviral protection in vivo. Analysis of bronchoalveolar lavage fluid (BALF) revealed that CYNK-001 reduced proinflammatory cytokines and chemokines highlighting CYNK-001’s anti-inflammatory actions in viral induced-lung injury. Furthermore, CYNK-001-treated mice had altered immune responses to IAV with reduced number of neutrophils in BALF yet increased number of CD8+ T cells in the BALF and lung compared to vehicle-treated mice. Our results demonstrate that CYNK-001 displays protective functions against IAV via its anti-inflammatory and immunomodulating activities, which leads to alleviation of disease burden and progression in a severe IAV-infected mice model. The potential of adoptive NK therapy for IAV infections warrants clinical investigation.

NK cells and monocytes modulate primary HTLV-1 infection.

We investigated the impact of monocytes, NK cells, and CD8+ T-cells in primary HTLV-1 infection by depleting cell subsets and exposing macaques to either HTLV-1 wild type (HTLV-1WT) or to the HTLV-1p12KO mutant unable to infect replete animals due to a single point mutation in orf-I that inhibits its expression. The orf-I encoded p8/p12 proteins counteract cytotoxic NK and CD8+ T-cells and favor viral DNA persistence in monocytes. Double NK and CD8+ T-cells or CD8 depletion alone accelerated seroconversion in all animals exposed to HTLV-1WT. In contrast, HTLV-1p12KO infectivity was fully restored only when NK cells were also depleted, demonstrating a critical role of NK cells in primary infection. Monocyte/macrophage depletion resulted in accelerated seroconversion in all animals exposed to HTLV-1WT, but antibody titers to the virus were low and not sustained. Seroconversion did not occur in most animals exposed to HTLV-1p12KO. In vitro experiments in human primary monocytes or THP-1 cells comparing HTLV-1WT and HTLV-1p12KO demonstrated that orf-I expression is associated with inhibition of inflammasome activation in primary cells, with increased CD47 “don’t-eat-me” signal surface expression in virus infected cells and decreased monocyte engulfment of infected cells. Collectively, our data demonstrate a critical role for innate NK cells in primary infection and suggest a dual role of monocytes in primary infection. On one hand, orf-I expression increases the chances of viral transmission by sparing infected cells from efferocytosis, and on the other may protect the engulfed infected cells by modulating inflammasome activation. These data also suggest that, once infection is established, the stoichiometry of orf-I expression may contribute to the chronic inflammation observed in HTLV-1 infection by modulating monocyte efferocytosis.

A mathematical model to describe antibody-dependent enhancement and assess the effect of limiting cloning for plasma cells in heterologous secondary dengue infection.

We propose a mathematical model to study the antibody-dependent enhancement (ADE) phenomenon. Here, we explore the interaction between macrophages, dengue virus and plasma cells, especially the effect of a limitation on plasma cell proliferation, which occurs due to immunological memory. The model has up to three equilibrium points: one virus-free equilibrium and two virus-presence equilibrium, depending on the value of two thresholds. We determine the existence regions for the model equilibrium points and their stability, a sensitivity analysis was performed in the model thresholds. Numerical simulations illustrate that ADE can occur even when the basic reproduction number is less than one.

Vγ2+ γδ T Cells in the Presence of Anti-CD40L Control Surgical Inflammation and Promote Skin Allograft Survival

γδ T cells represent a small fraction of total T cells in the body and do not use classical polymorphic major histocompatibility complex‒loaded peptides for mounting an immune response. The importance of the effector and regulatory function of γδ T cells in infections, autoimmunity, and tumor models are well characterized. In this study, we investigated the mechanistic role of γδ T cells in costimulatory blockade‒induced transplantation tolerance. We used donor-specific transfusion and anti-CD40L treatment in C57BL/6 mice to induce tolerance to BALB/c skin allografts. We show that depletion of γδ T cells, specifically Vγ2+ γδ T cells, led to the acute rejection of skin allografts despite tolerogen treatment. Tolerogen treatment promoted CD39+Vγ2+ γδ T cells and suppressed IFN-γ‒producing Vγ2+ γδ T cells in the spleen and allografts. Vγ2+ γδ T cells isolated from tolerized mice suppress T helper type 1 cell differentiation. Adoptive transfer of these regulatory Vγ2+ γδ T cells prolonged the survival of allografts in an untreated recipient and Tcrδ‒/‒ mice. Together, our data show that the Vγ2+ subset promotes costimulatory blockade‒induced survival of skin allografts and that tolerogenic Vγ2+ T cells can be used as an adoptive cellular therapy to promote the survival of allografts.

Autocrine and paracrine IL-2 signals collaborate to regulate distinct phases of CD8 Tcell memory.

Differential interleukin-2 (IL-2) signaling and production are associated with disparate effector and memory fates. Whether the IL-2 signals perceived by CD8 Tcells come from autocrine or paracrine sources, the timing of IL-2 signaling and their differential impact on CD8 Tcell responses remain unclear. Using distinct models of germline and conditional IL-2 ablation in post-thymic CD8 Tcells, this study shows that paracrine IL-2 is sufficient to drive optimal primary expansion, effector and memory differentiation, and metabolic function. In contrast, autocrine IL-2 is uniquely required during primary expansion to program robust secondary expansion potential in memory-fated cells. This study further shows that IL-2 production by antigen-specific CD8 Tcells is largely independent of CD4 licensing of dendritic cells (DCs) in inflammatory infections with robust DC activation. These findings bear implications for immunizations and adoptive Tcell immunotherapies, where effector and memory functions may be commandeered through IL-2 programming.

Low dose radiation therapy attenuates ACE2 depression and inflammatory cytokines induction by COVID-19 viral spike protein in human bronchial epithelial cells

Purpose: Low-dose radiation therapy (LDRT) is an evidence-based anti-inflammatory treatment. In anti-COVID-19, our study suggests that low to moderate dose radiation of < 1.5 Gy can inhibit the induction of inflammatory cytokine and attenuate the ACE2 depression induced by spike protein in human bronchial epithelial cells in COVID-19 infection. Our study provided further mechanistic evidence to support LDRT as a cost-effective treatment for COVID-19 to relieve the severe inflammatory reaction and lung injury. Methods and materials: A cellular model was created by treating human bronchial epithelial cells (BEP2D) with SARS-CoV-2 spike protein. We used the qRT-PCR and ELISA analysis to identify the production of inflammatory cytokines. The BEP2D control cells and the spike-treated cells were irradiated using a single low to moderate dose radiation of 0.5 Gy, 1 Gy, and 1.5 Gy. The inflammatory cytokines and ACE2 expression were detected at different time points. Results: The soluble SARS-CoV-2 spike protein stimulated the formation of inflammatory cytokines IL-6 and TNF-α while reducing the ACE2 protein expression in human bronchial epithelial cells. A single low to moderate dose exposure of 0.5 Gy, 1 Gy, and 1.5 Gy could attenuate the IL-6 and TNF-α induction and rescue the depression of ACE2 by spike protein. Moreover, the spike protein increased the proteolytic degradation of ACE2 protein by promoting NEDD4-mediated ubiquitination of ACE2. Conclusions: The low-dose radiation can attenuate ACE2 depression and inflammatory response produced in the targeted human bronchial epithelial cells by spike protein. This coordinating effect of LDRT may relieve the severe inflammatory reaction and lung injury in COVID-19 patients.

Age-associated B cells in viral infection.

Age-associated B cells (ABCs) are a recently identified, unique B cell population that displays both protective and pathogenic characteristics, depending on the context. A major role of ABCs is to protect from viral infection. ABCs expand during an array of viral infections and display various functional capacities, including secretion of antibodies and activation of T cells. Following resolution of infection, ABCs appear to persist and play a crucial role in memory and recall responses. Here, we review the currently understanding of ABCs in the antiviral response in both humans and mice. We discuss avenues for future research, including the impact of sex on the ABC population and heterogeneity of ABCs between contexts.

Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions.

Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer’s and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one important cause of age-related morbidity and mortality, which may extend beyond its role in infectious disease. One aspect of immunosenescence that has received less attention is age-related natural killer (NK) cell dysfunction, characterized by reduced cytokine secretion and decreased target cell cytotoxicity, accompanied by and despite an increase in NK cell numbers with age. Moreover, recent studies have revealed that NK cells are the central actors in the immunosurveillance of senescent cells, whose age-related accumulation is itself a probable contributor to the chronic sterile low-grade inflammation developed with aging (“inflammaging”). NK cell dysfunction is therefore implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age. This review will focus on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging. Understanding the factors driving and enforcing NK cell aging may potentially lead to therapies countering age-related diseases and underlying drivers of the biological aging process itself.

A Nodule-Localized Small Heat Shock Protein GmHSP17.1 Confers Nodule Development and Nitrogen Fixation in Soybean

Small heat shock proteins (sHSPs) are ubiquitous proteins present in all organisms. The sHSPs are not only upregulated under heat shock as well as other stresses but also are expressed in unstressed cells, indicating quite diverse functions of sHSPs. However, there is little known about the role of sHSPs in nodulation and nitrogen fixation in soybean. In this study, we cloned a candidate protein of sHSP, GmHSP17.1, from proteome of nodule and analyzed its function in soybean nodulation. We found that GmHSP17.1 was a cytosolic protein and preferentially expressed during nodule development. An overexpression of GmHSP17.1 in composite transgenic plants showed increases in nodule number, fresh weight, nodule size, area of infection cells, and nitrogenase activity, and subsequently promoted the content of nitrogen and growth of soybean plants. While GmHSP17.1 RNA interference (RNAi) lines showed significantly impaired nodule development and nitrogen fixation efficiency. Through liquid chromatography-tandem mass spectrometry (LC-MS/MS), GmRIP1 was identified as the first potential target of GmHSP17.1, and was shown to be specifically expressed in soybean nodules. The interaction between GmHSP17.1 and GmRIP1 was further confirmed by yeast-two hybrid (Y2H), bimolecular fluorescence complementation (BiFC) in vivo and pull-down assay in vitro. Furthermore, peroxidase activity was markedly increased in GmHSP17.1 overexpressed nodules and decreased in RNAi lines. As a result, the reactive oxygen species (ROS) content greatly decreased in GmHSP17.1 overexpression lines and increased in suppression lines. Taken together, we conclude that GmHSP17.1 plays an important role in soybean nodulation through interacting with GmRIP1. Our results provide foundation for studying the mechanism of nitrogen fixation and for the genetics improvement of legume plants.

Negative Regulation and Protective Function of Natural Killer Cells in HIV Infection: Two Sides of a Coin.

Natural killer (NK) cells play an important immunologic role, targeting tumors and virus-infected cells; however, NK cells do not impede the progression of human immunodeficiency virus (HIV) infection. In HIV infection, NK cells exhibit impaired functions and negatively regulate other immune cell responses, although NK cells can kill HIV-infected cells and thereby suppress HIV replication. Considerable recent research has emerged regarding NK cells in the areas of immune checkpoints, negative regulation, antibody-dependent cell-mediated cytotoxicity and HIV reservoirs during HIV infection; however, no overall summary of these factors is available. This review focuses on several important aspects of NK cells in relation to HIV infection, including changes in NK cell count, subpopulations, and immune checkpoints, as well as abnormalities in NK cell functions and NK cell negative regulation. The protective function of NK cells in inhibiting HIV replication to reduce the viral reservoir and approaches for enhancing NK cell functions are also summarized.

Comparison of Serum Levels of Autophagy -Related Gene 5 in Patients With/ Without Helicobacter Pylori Infection

Introduction: Laboratory studies have shown that gastric epithelial infection cells with Helicobacter pylori (H. pylori) infection increase the rate of autophagy. Disruption of this process causes various diseases, including cancer. Objective: This study aimed to evaluate the serum level of Autophagy -Related Gene 5 (ATG5) in individuals with and without H. pylori infection. Materials and Methods: This pilot cross-sectional analytical study was performed in 2018 for 44 individuals aged 35-50 years referred to the endoscopy ward of Razi Hospital of Rasht. Age, sex, body mass index, smoking, and symptoms were recorded in a questionnaire. Based on rapid urease test and pathology in two groups of 22 people, the presence and absence of H. pylori infection were examined. Serum ATG5 levels were quantitatively assessed by ELISA with an EIAab kit made in the USA. Results: In this study, 56.8% were male, 77.3% were over 40 years old, 52.3% had a BMI of less than 5 and 70.5% were smokers. The mean (±SD) of ATG5 in individuals with, and without H. pylori were (63.5 ± 15.4) and (57.1 ± 18.9), respectively (P &gt;0.05). The mean ATG5 factor was higher in women than men (P = 0.047). Conclusion: In the present study, ATG5 was not significant in those with and without H. pylori. It is recommended a study be performed in larger sample size and based on a comparison of gastrointestinal lesions.

Type I conventional dendritic cells relate to disease severity in virus-induced asthma exacerbations.

RationaleRhinoviruses are the major precipitant of asthma exacerbations and individuals with asthma experience more severe/prolonged rhinovirus infections. Concurrent viral infection and allergen exposure synergistically increase exacerbation risk. Although dendritic cells orchestrate immune responses to both virus and allergen, little is known about their role in viral asthma exacerbations.ObjectivesTo characterize dendritic cell populations present in the lower airways, and to assess whether their numbers are altered in asthma compared to healthy subjects prior to infection and during rhinovirus‐16 infection.MethodsModerately‐severe atopic asthmatic patients and healthy controls were experimentally infected with rhinovirus‐16. Bronchoalveolar lavage was collected at baseline, day 3 and day 8 post infection and dendritic cells isolated using fluorescence activated cell sorting.Measurements and Main ResultsNumbers of type I conventional dendritic cells, which cross prime CD8+ T helper cells and produce innate interferons, were significantly reduced in the lower airways of asthma patients compared to healthy controls at baseline. This reduction was associated serum IgE at baseline and with reduced numbers of CD8+ T helper cells and with increased viral replication, airway eosinophils and reduced lung function during infection. IgE receptor expression on lower airway plasmacytoid dendritic cells was significantly increased in asthma, consistent with a reduced capacity to produce innate interferons.ConclusionsReduced numbers of anti‐viral type I conventional dendritic cells in asthma are associated with adverse outcomes during rhinovirus infection. This, with increased FcεR1α expression on lower airway plasmacytoid DCs could mediate the more permissive respiratory viral infection observed in asthma patients.

Emerging role of γδ T cells in protozoan infection and their potential clinical application.

γδ T cells are thymus derived heterogeneous and unconventional T- lymphocyte expressing TCR γ (V γ9) and TCRδ (Vδ2) chain and play an important role in connecting innate and adaptive armaments of immune response. These cells can recognize wide ranges of antigens even without involvement of major histocompatibility complex and exert their biological functions by cytotoxicity or activating various types of immune cells. In recent past, γδ T cells have emerged as an important player during protozoa infection and rapidly expand after exposure with them. They have also been widely studied in vaccine induced immune response against many bacterial and protozoan infections with improved clinical outcome. In this review, we will discuss the various roles of γδ T cells in immunity against malaria and leishmaniasis, the two important protozoan diseases causing significant mortality and morbidity throughout the world.

Investigation of bovine coronavirus strain CV-315 cultural properties

The purpose of this study was to investigate the features of cultivation of bovine coronavirus strain CV-315 isolated in Ukraine from a calf with coronavirus infection and to select optimal methods of virus cultivation to obtain viral material with the highest possible titers of infectious activity in order to develop manufacturing technology of means of immunoprophylaxis and specific diagnostics. During the study, the influence of a number of factors on the accumulation of strain CV-315 was studied: the presence and concentration of trypsin in the nutrient medium, the effect of fetal bovine serum, the degree of cell culture monolayer during virus infection, also the virus dose, temperature and the term of cultivation. According to the results, it was established that bovine coronavirus strain CV-315 has the highest infectious activity when cultured for 72 hours before the manifestation of CPE of 70–80%, without the addition of trypsin and fetal bovine serum content of 2% at 37±0.5°C. It was also found that the optimal infective dose is 0.1–0.01 viral particles per cell for infection of the fully formed monolayer of MDBK cell culture. The obtained results will be used in the development of veterinary vaccines against bovine coronavirus.

A56 TUFT CELL RESPONSES DURING ACUTE- AND LATE-STAGE GIARDIA INFECTION

BackgroundEpithelial tuft cells can detect and respond to enteric infections and appear to help clear some intestinal parasites. Through tuft cell luminal surface receptors, tuft cells can sense ligands directly supplied by a parasite, or indirectly via excretory/secretory products. We hypothesize that microbiome alterations may also modulate tuft cell-derived gut responses. Tuft cells release the alarmin cytokine IL-25 which, upon acting on type 2 innate lymphoid cells (ILC2), ultimately lead to tuft and goblet cell hyperplasia. Upon helminth infections, tuft and goblet cell hyperplasia occurred concurrently, and coincided with the peak of infection. The role of tuft cells in infections with the enteric protozoan parasite Giardia sp. is unknown. The aim of our study is to characterize how tuft cells may be implicated in the pathophysiology of giardiasis, in an attempt to uncover novel regulatory pathways of intestinal physiology.AimsIn this study, we aim to characterise the tuft cell response to Giardia infection during acute and late stages of infection and to assess goblet cell hyperplasia.Methods5–7-week-old C57BL/6 mice and tuft cell-deficient mice ( Pou2f3-/-) were orally gavaged with 5x104Giardia muris trophozoites and scarified at days 4, 11 and 21 post-infection. Parasite burden was assessed in the duodenum. Immunofluorescence (IF) staining of doublecortin-like kinase 1 (DCLK1) – a marker of tuft cells – was performed on C57BL/6 mice jejunum tissue sections and the number of tuft cells was quantified. Goblet cells were quantified in PAS/AB-stained jejunum sections. Quantitative PCR (qPCR) was performed on Dclk1, the epithelial secretory cell transcription factor Atoh1, and the mucus gene Muc2.Results G. muris infected C57BL/6 mice displayed high parasite load at days 4 ( p<0.05) and 11 ( p<0.05), with no or low parasite burden at day 21 ( p<0.05). Pou2f3-/- mice showed less robust parasite burden at days 4 and 11, and similar low parasite burden at day 21, compared to WT mice. At day 21, tuft cell (DCLK1+) counts ( p<0.05) and Dclk1 mRNA expression levels were increased in Giardia infected mice in the jejunum. Goblet cell number and Atoh1 and Muc2 expression were increased at day 4 post-infection.ConclusionsThe data demonstrate that tuft cells expand late in Giardia infection, suggesting that upon parasite infection, tuft cells may possess roles in tissue repair or clearance of infection. Tuft cell-deficient mice ( Pou2f3-/-) had lower parasite burden early in Giardia infection, counter-intuitively suggesting that tuft cells may facilitate trophozoite colonization, further highlighting the novelty of these findings. The crosstalk between tuft cells, Giardia, and other host responses during acute and late stages of infection remain to be fully characterised.Funding AgenciesNSERC

The Multifaceted Roles of Mast Cells in Immune Homeostasis, Infections and Cancers.

Mast cells (MCs) play important roles in normal immune responses and pathological states. The location of MCs on the boundaries between tissues and the external environment, including gut mucosal surfaces, lungs, skin, and around blood vessels, suggests a multitude of immunological functions. Thus, MCs are pivotal for host defense against different antigens, including allergens and microbial pathogens. MCs can produce and respond to physiological mediators and chemokines to modulate inflammation. As long-lived, tissue-resident cells, MCs indeed mediate acute inflammatory responses such as those evident in allergic reactions. Furthermore, MCs participate in innate and adaptive immune responses to bacteria, viruses, fungi, and parasites. The control of MC activation or stabilization is a powerful tool in regulating tissue homeostasis and pathogen clearance. Moreover, MCs contribute to maintaining the homeostatic equilibrium between host and resident microbiota, and they engage in crosstalk between the resident and recruited hematopoietic cells. In this review, we provide a comprehensive overview of the functions of MCs in health and disease. Further, we discuss how mouse models of MC deficiency have become useful tools for establishing MCs as a potential cellular target for treating inflammatory disorders.

Establishment and Genetic Manipulation of Murine Hepatocyte Organoids.

The liver is the largest organ in mammals. It plays an important role in glucose storage, protein secretion, metabolism and detoxification. As the executor for most of the liver functions, primary hepatocytes have limited proliferating capacity. This requires the establishment of ex vivo hepatocyte expansion models for liver physiological and pathological research. Here, we isolated murine hepatocytes by two steps of collagenase perfusion and established a 3D organoid culture as the 'mini-liver' to recapitulate cell-cell interactions and physical functions. The organoids consist of heterogeneous cell populations including progenitors and mature hepatocytes. We introduce the process in detailed to isolate and culture the murine hepatocytes or fetal hepatocyte to form organoids within 2-3 weeks and show how to passage them by mechanically pipetting up and down. In addition, we will also introduce how to digest the organoids into single cells for lentivirus infection of shRNA/ectopic construction, siRNA transfection and CRISPR-Cas9 engineering. The organoids can be used for drug screens, disease modelling, and basic liver research by modeling liver biology and pathobiology.

The Immunological Role of Vascular and Lymphatic Endothelial Cells in Filarial Infections.

Simple SummaryThe endothelium is a monolayer of cells forming a thin membrane that lines the inside of blood vessels. These cells release molecules that regulate vascular relaxation, contraction, and can control blood clotting and the immune response. During infections with filarial nematodes, common parasites of humans and animals, the endothelium is believed to play a key role in the communication between the host and the parasite, since the embryonic stage of filaroids is distributed in the bloodstream. Therefore, this review aims to gather research from different scientists in order to better understand the host immune response in infections with filarial nematodes.The embryonic stage of filarial nematodes, or microfilariae (Mf), shows daily and seasonal periodicity that requires their migration through blood vessels into the lungs, where they are sequestered when not circulating in the peripheral blood. Therefore, Mf and the host endothelium are likely in a permanent state of hide and seek. Interestingly, filarial nematodes co-cultured in media with a murine endothelial cell line survive eight times longer than those cultured in media alone. This suggests that the endothelium is an important element of the immune response in filarial nematodes, perversely promoting their survival in the host. In this review, we will focus on potential pathways involved in the relationship between filarial nematodes and the host endothelium, including the role of endothelial ICAM/VCAM/PECAM adhesion molecules, surface markers involved in the passage of Mf through host tissue, anti-thrombolic effects caused by the presence of filarial nematodes (including plasmins), endothelial cell proliferation (VEGF), and other aspects of the immune activation of the endothelium. The aim of this review is to merge the knowledge about the cross-talk between Mf of different filarial nematode species and endothelial cells (EC), thus allowing a better understanding of the mechanism of these parasitic infections.