Host Immune System Response Research Articles

Host Innate and Adaptive Immunity Against African Swine Fever Virus Infection

Africa swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a highly contagious hemorrhagic disease that can result in up to 100% lethality in both wild and domestic swine, regardless of breed or age. The ongoing ASF pandemic poses significant threats to the pork industry and food security, with serious implications for the sanitary and socioeconomic system. Due to the limited understanding of ASFV pathogenesis and immune protection mechanisms, there are currently no safe and effective vaccines or specific treatments available, complicating efforts for prevention and control. This review summarizes the current understanding of the intricate interplay between ASFV and the host immune system, encompassing both innate and adaptive immune responses to ASFV infection, as well as insights into ASFV pathogenesis and immunosuppression. We aim to provide comprehensive information to support fundamental research on ASFV, highlighting existing gaps and suggesting future research directions. This work may serve as a theoretical foundation for the rational design of protective vaccines against this devastating viral disease.

Quantum Dot-Based Nanosensors for In Vitro Detection of Mycobacterium tuberculosis.

Despite the existing effective treatment methods, tuberculosis (TB) is the second most deadly infectious disease, its carriers in the latent and active phases accounting for more than 20% of the world population. An effective method for controlling TB and reducing TB mortality is regular population screening aimed at diagnosing the latent form of TB and taking preventive and curative measures. Numerous methods allow diagnosing TB by directly detecting Mycobacterium tuberculosis (M.tb) biomarkers, including M.tb DNA, proteins, and specific metabolites or antibodies produced by the host immune system in response to M.tb. PCR, ELISA, immunofluorescence and immunochemical analyses, flow cytometry, and other methods allow the detection of M.tb biomarkers or the host immune response to M.tb by recording the optical signal from fluorescent or colorimetric dyes that are components of the diagnostic systems. Current research in biosensors is aimed at increasing the sensitivity of detection, a promising approach being the use of fluorescent quantum dots as brighter and more photostable optical tags. Here, we review current methods for the detection of M.tb biomarkers using quantum dot-based nanosensors and summarize data on the M.tb biomarkers whose detection can be made considerably more sensitive by using these sensors.

MicroRNA bmo-miR-31-5p inhibits apoptosis and promotes BmNPV proliferation by targeting the CYP9e2 gene of Bombyx mori.

Bombyx mori nuclear polyhedrosis virus (BmNPV), as a typical baculovirus, is the primary pathogen that infects the silkworm B. mori, a lepidopteran species. Owing to the high biological safety of BmNPV in infecting insects, it is commonly utilized as a biological insecticide for pest control. Apoptosis is important in the interaction between the host and pathogenic microorganisms. MicroRNAs (miRNAs) influence immune responses and promote stability of the immune system via apoptosis. Therefore, the study of apoptosis-related miRNA in silkworms during virus infection can not only provide support for standardizing the prevention and control of diseases and insect pests, but also reduce the economic losses to sericulture caused by the misuse of biological pesticides. Through transcriptome sequencing, we identified a miRNA, miR-31-5p, and demonstrated that it can inhibit apoptosis in silkworm cells and promote the proliferation of BmNPV in BmE-SWU1 cells. We identified a target gene of miR-31-5p, B. mori cytochrome P450 9e2 (BmCYP9e2), and demonstrated that it can promote apoptosis in silkworm cells and inhibit the proliferation of BmNPV. Moreover, we constructed transgenic silkworm strains with miR-31-5p knockout and confirmed that they can inhibit the proliferation of BmNPV. These data indicate that miR-31-5p may exert functions of inhibiting apoptosis and promoting virus proliferation by regulating BmCYP9e2. The findings demonstrate how miRNAs influence host cell apoptosis and how they are involved in the host immune system response to viruses, providing important insights into the applications of biological insecticides for pest control. © 2024 Society of Chemical Industry.

Morphological analysis and lipid composition of the stable fly Stomoxys calcitrans salivary glands reinforce important features of feeding behaviour.

Stomoxys calcitrans L. (Diptera: Muscidae), the stable fly, is a hematophagous insect of great veterinary importance, because it is a mechanical vector of diverse pathogens in livestock. The saliva of blood-feeding insects presents important pharmacologically active molecules that impair blood clotting, promote vasodilation and modulate the host immune system response, crucial processes for successful feeding. These properties also enable pathogens' transmission. In the present work, we describe an efficient protocol to dissect S. calcitrans salivary glands, their morphological characteristics and lipid profile. The mean length of the tubular gland is 3.23 mm with a bulbous posterior end and a narrow anterior end. Histological analysis revealed a monolayer of large polygonal epithelial cells with voluminous nuclei and high lipid content in their cytoplasm. Ultrastructural analysis showed that the epithelium is rich in mitochondria, free ribosomes, Golgi complex cisternae, presenting a great extension of rough endoplasmic reticulum that contains an electron-dense material. Lipid analysis by thin-layer chromatography showed that neutral fatty acids and phosphatidylcholine are predominant in the fly salivary glands. Lysophosphatidylcholine, an important signalling biomolecule involved in different metabolic processes, including host's immunomodulation and pathogens proliferation and differentiation, is also present.

Exploring the impression of TRIM25 gene expression on COVID-19 severity and SARS-CoV-2 viral replication

BackgroundThere are numerous human genes associated with viral infections, and their identification in specific populations can provide suitable therapeutic targets for modulating the host immune system response and better understanding the viral pathogenic mechanisms. Many antiviral signaling pathways, including Type I interferon and NF-κB, are regulated by TRIM proteins. Therefore, the identification of TRIM proteins involved in COVID-19 infection can play a significant role in understanding the innate immune response to this virus. MethodsIn this study, the expression of TRIM25 gene was evaluated in a blood sample of 330 patients admitted to the hospital (142 patients with severe disease and 188 patients with mild disease) as well as in 160 healthy individuals. The relationship between its expression and the severity of COVID-19 disease was assessed and compared among the study groups by quantitative Real-time PCR technique. The statistical analysis of the results demonstrated a significant reduction in the expression of TRIM25 in the group of patients with severe infection compared to those with mild infection. Furthermore, the impact of increased expression of TRIM25 gene in HEK-293 T cell culture was investigated on the replication of attenuated SARS-CoV-2 virus. ResultsThe results of Real-time PCR, Western blot for the viral nucleocapsid gene of virus, and CCID50 test indicated a decrease in virus replication in these cells. The findings of this research indicated that the reduced expression of the TRIM25 gene was associated with increased disease severity of COVID-19 in individuals. Additionally, the results suggested the overexpression of TRIM25 gene can impress the replication of attenuated SARS-CoV-2 and the induction of beta-interferon. ConclusionTRIM25 plays a critical role in controlling viral replication through its direct interaction with the virus and its involvement in inducing interferon during the early stages of infection. This makes TRIM25 a promising target for potential therapeutic interventions.

Radiation-induced eCIRP impairs macrophage bacterial phagocytosis.

Macrophages are essential immune cells for host defense against bacterial pathogens after radiation injury. However, the role of macrophage phagocytosis in infection following radiation injury remains poorly examined. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern that dysregulates host immune system responses such as phagocytosis. We hypothesized that radiation-induced eCIRP release impairs macrophage phagocytosis of bacteria. Adult healthy mice were exposed to 6.5-Gy total body irradiation (TBI). Primary peritoneal macrophages isolated from adult healthy mice were exposed to 6.5-Gy radiation. eCIRP-neutralizing monoclonal antibody (mAb) was added to the cell culture prior to irradiation. Bacterial phagocytosis by peritoneal macrophages was assessed using pHrodo Green-labeled E. coli 7 days after irradiation ex vivo and in vitro. Bacterial phagocytosis was also assessed after treatment with recombinant murine CIRP (rmCIRP). Rac1 and ARP2 protein expression in cell lysates and eCIRP levels in the peritoneal lavage were assessed by Western blotting. Bacterial phagocytosis by peritoneal macrophages was significantly decreased after irradiation compared to controls ex vivo and in vitro. Rac1 and ARP2 expression in the peritoneal macrophages were downregulated after TBI. TBI significantly increased eCIRP levels in the peritoneal cavity. rmCIRP significantly decreased bacterial phagocytosis in a dose-dependent manner. eCIRP mAb restored bacterial phagocytosis by peritoneal macrophages after irradiation. Ionizing radiation exposure impairs bacterial phagocytosis by macrophages after irradiation. Neutralization of eCIRP restores the phagocytic ability of macrophages after irradiation. Our findings elucidate a novel mechanism of immune dysfunction and provide a potential new therapeutic approach for limiting infection after radiation injury.

Understanding host immune responses in Clostridioides difficile infection: Implications for pathogenesis and immunotherapy.

Clostridioides difficile (C. difficile) is the predominant causative agent of nosocomial diarrhea worldwide. Infection with C. difficile occurs due to the secretion of large glycosylating toxin proteins, which can lead to toxic megacolon or mortality in susceptible hosts. A critical aspect of C. difficile's biology is its ability to persist asymptomatically within the human host. Individuals harboring asymptomatic colonization or experiencing a single episode of C. difficile infection (CDI) without recurrence exhibit heightened immune responses compared to symptomatic counterparts. The significance of these immune responses cannot be overstated, as they play critical roles in the development, progression, prognosis, and outcomes of CDI. Nonetheless, our current comprehension of the immune responses implicated in CDI remains limited. Therefore, further investigation is imperative to elucidate their underlying mechanisms. This review explores recent advancements in comprehending CDI pathogenesis and how the host immune system response influences disease progression and severity, aiming to enhance our capacity to develop immunotherapy-based treatments for CDI.

Biomimetic Nanovehicle-Enabled Targeted Depletion of Intratumoral Fusobacterium nucleatum Synergizes with PD-L1 Blockade against Breast Cancer.

Immune checkpoint blockade (ICB) therapy has been approved for breast cancer (BC), but clinical response rates are limited. Recent studies have shown that commensal microbes colonize a variety of tumors and are closely related to the host immune system response. Here, we demonstrated that Fusobacterium nucleatum (F.n), which is prevalent in BC, creates an immunosuppressive tumor microenvironment (ITME) characterized by a high-influx of myeloid cells that hinders ICB therapy. Administering the antibiotic metronidazole in BC can deplete F.n and remodel the ITME. To prevent an imbalance in the systemic microbiota caused by antibiotic administration, we designed a biomimetic nanovehicle for on-site antibiotic delivery inspired by F.n homing to BC. Additionally, ferritin-nanocaged doxorubicin was coloaded into this nanovehicle, as immunogenic chemotherapy has shown potential for synergy with ICB. It has been demonstrated that this biomimetic nanovehicle can be precisely homed to BC and efficiently eliminate intratumoral F.n without disrupting the diversity and abundance of systemic microbiota. This ultimately remodels the ITME, improving the therapeutic efficacy of the PD-L1 blocker with a tumor inhibition rate of over 90% and significantly extending the median survival of 4T1 tumor-bearing mice.

Current Advances in Graft-versus-host Disease After Intestinal Transplantation.

Graft-versus-host disease (GvHD) remains a potentially fatal complication following intestinal transplant (ITx). Over the past decade, advances in the understanding of the pathophysiology of this complex immunological phenomenon have led to the reassessment of the host systemic immune response and have created a gateway for novel preventive and therapeutic strategies. Although sufficient evidence dictates the use of corticosteroids as a first-line option, the treatment for refractory disease remains contentious and lacks a standardized therapeutic approach. Timely diagnosis remains crucial, and the advent of chimerism detection and immunological biomarkers have transformed the identification, prognostication, and potential for survival after GvHD in ITx. The objectives of the following review aim to discuss the clinical and diagnostic features, pathophysiology, advances in immune biomarkers, as well as therapeutic opportunities in the prevention and treatment of GvHD in ITx.

Genetic Susceptibility to Fungal Infections.

Reports of fungal infections have increased over the past decades, making them a major threat to human health. In this study, we review the effects of genetic defects on susceptibility to fungal diseases. To identify all relevant literature, we searched Google Scholar, PubMed, and Scopus and profiled studies published between 2008 and 2021. The results of several studies conducted on this subject have shown the significant effects of genetic variations such as hyper-IgE syndrome, Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome, dectin-1 deficiency, CARD9 mutations, STAT1 mutations, and IL17 mutationson the host immune system's response, which has an important impact on susceptibility to fungal infections. The underlying immune system-related genetic profile affects the susceptibility of individuals to different fungal infections; therefore, this subject should be further studied for better treatment of fungal diseases.

Antibodies to coagulase of Staphylococcus aureus crossreact to Efb and reveal different binding of shared fibrinogen binding repeats.

Staphylococcus aureus pathology is caused by a plethora of virulence factors able to combat multiple host defence mechanisms. Fibrinogen (Fg), a critical component in the host coagulation cascade, plays an important role in the pathogenesis of this bacterium, as it is the target of numerous staphylococcal virulence proteins. Amongst its secreted virulence factors, coagulase (Coa) and Extracellular fibrinogen-binding protein (Efb) share common Fg binding motives and have been described to form a Fg shield around staphylococcal cells, thereby allowing efficient bacterial spreading, phagocytosis escape and evasion of host immune system responses. Targeting these proteins with monoclonal antibodies thus represents a new therapeutic option against S. aureus. To this end, here we report the selection and characterization of fully human, sequence-defined, monoclonal antibodies selected against the C-terminal of coagulase. Given the functional homology between Coa and Efb, we also investigated if the generated antibodies bound the two virulence factors. Thirteen unique antibodies were isolated from naïve antibodies gene libraries by antibody phage display. As anticipated, most of the selected antibodies showed cross-recognition of these two proteins and among them, four were able to block the interaction between Coa/Efb and Fg. Furthermore, our monoclonal antibodies could interact with the two main Fg binding repeats present at the C-terminal of Coa and distinguish them, suggesting the presence of two functionally different Fg-binding epitopes.

Developing Oncolytic Viruses for the Treatment of Cervical Cancer.

Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for several patients leading to serious side effects, which can have negative implications on the quality of life of women. Therefore, there is an urgent need for the development of innovative and effective treatment options. Oncolytic viruses can eventually become effective biological agents, since they preferentially infect and kill cancer cells, while leaving the normal tissue unaffected. Moreover, they are also able to leverage the host immune system response to limit tumor growth. This review aims to systematically describe and discuss the different types of oncolytic viruses generated for targeting cervical cancer cells, as well as the outcome of the combination of virotherapy with conventional therapies. Although many preclinical studies have evaluated the therapeutic efficacy of oncolytic viruses in cervical cancer, the number of clinical trials so far is limited, while their oncolytic properties are currently being tested in clinical trials for the treatment of other malignancies.

β3-adrenergic receptor on tumor-infiltrating lymphocytes sustains IFN-γ-dependent PD-L1 expression and impairs anti-tumor immunity in neuroblastoma

Neuroblastoma (NB) is a heterogeneous extracranial tumor occurring in childhood. A distinctive feature of NB tumors is their neuroendocrine ability to secrete catecholamines, which in turn, via β-adrenergic receptors ligation, may affect different signaling pathways in tumor microenvironment (TME). It was previously demonstrated that specific antagonism of β3-adrenergic receptor (β3-AR) on NB tumor cells affected tumor growth and progression. Here, in a murine syngeneic model of NB, we aimed to investigate whether the β3-AR modulation influenced the host immune system response against tumor. Results demonstrated that β3-AR antagonism lead to an immune response reactivation, partially dependent on the PD-1/PD-L1 signaling axis involvement. Indeed, β3-AR blockade on tumor-infiltrating lymphocytes (TILs) dampened their ability to secrete IFN-γ, which in turn reduced the PD-L1 expression, caused by TILs infiltration, on NB tumor cells. Further investigations, through a genomic analysis on NB patients, showed that high ADRB3 gene expression correlates with worse clinical outcome compared to the low expression group, and that ADRB3 gene expression affects different immune-related pathways. Overall, results indicate that β3-AR in NB TME is able to modulate the interaction between tumor and host immune system, and that its antagonism hits multiple pro-tumoral signaling pathways.

Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include smallpox and influenza, with efficacious therapeutics utilized to reduce overall disease burden through effectively targeting a competent host immune system response. The immune system is composed of primary/secondary lymphoid structures with initially eight types of immune cell types, and many other subtypes, traversing cell membranes utilizing cell signaling cascades that contribute towards clearance of pathogenic proteins. Other proteins discussed include cluster of differentiation (CD) markers, major histocompatibility complexes (MHC), pleiotropic interleukins (IL), and chemokines (CXC). The historical concepts of host immunity are the innate and adaptive immune systems. The adaptive immune system is represented by T cells, B cells, and antibodies. The innate immune system is represented by macrophages, neutrophils, dendritic cells, and the complement system. Other viruses can affect and regulate cell cycle progression for example, in cancers that include human papillomavirus (HPV: cervical carcinoma), Epstein-Barr virus (EBV: lymphoma), Hepatitis B and C (HB/HC: hepatocellular carcinoma) and human T cell Leukemia Virus-1 (T cell leukemia). Bacterial infections also increase the risk of developing cancer (e.g., Helicobacter pylori). Viral and bacterial factors can cause both morbidity and mortality alongside being transmitted within clinical and community settings through affecting a host immune response. Therefore, it is appropriate to contextualize advances in single cell sequencing in conjunction with other laboratory techniques allowing insights into immune cell characterization. These developments offer improved clarity and understanding that overlap with autoimmune conditions that could be affected by innate B cells (B1+ or marginal zone cells) or adaptive T cell responses to SARS-CoV-2 infection and other pathologies. Thus, this review starts with an introduction into host respiratory infection before examining invaluable cellular messenger proteins and then individual immune cell markers.

Gut Microbial-Derived Metabolites as Immune Modulators of T Helper 17 and Regulatory T Cells

The gut microbiota and its derived metabolites greatly impact the host immune system, both innate and adaptive responses. Gut dysbiosis and altered levels of microbiota-derived metabolites have been described in several immune-related and immune-mediated diseases such as intestinal bowel disease, multiple sclerosis, or colorectal cancer. Gut microbial-derived metabolites are synthesized from dietary compounds ingested by the host or host-produced metabolites, and additionally, some bacterial products can be synthesized de novo. In this review, we focus on the two first metabolites families including short-chain fatty acids, indole metabolites, polyamines, choline-derived compounds, and secondary bile acids. They all have been described as immunoregulatory molecules that specifically affect the adaptive immune system and T helper 17 and regulatory T cells. We discuss the mechanisms of action and the consequences in health and diseases related to these gut microbial-derived metabolites. Finally, we propose that the exogenous administration of these molecules or other compounds that bind to their immunoregulatory receptors in a homologous manner could be considered therapeutic approaches.

The Immune Microenvironment in Basal Cell Carcinoma.

The immune system plays a key role in the suppression and progression of basal cell carcinoma (BCC). The primary aetiological factor for BCC development is exposure to ultraviolet radiation (UVR) which, particularly in lighter Fitzpatrick skin types, leads to the accumulation of DNA damage. UVR has roles in the generation of an immunosuppressive environment, facilitating cancer progression. Rates of BCC are elevated in immunosuppressed patients, and BCC may undergo spontaneous immune-mediated regression. Histologic and immunohistochemical profiling of BCCs consistently demonstrates the presence of an immune infiltrate and associated immune proteins. Early studies of immune checkpoint inhibitors reveal promising results in BCC. Therefore, the host immune system and tumor responses to it are important in BCC pathogenesis. Understanding these interactions will be beneficial for disease prognostication and therapeutic decisions.

Deep Learning of Dual Plasma Fingerprints for High-Performance Infection Classification.

Infection classification is the key for choosing the proper treatment plans. Early determination of the causative agents is critical for disease control. Host responses analysis can detect variform and sensitive host inflammatory responses to ascertain the presence and type of the infection. However, traditional host-derived inflammatory indicators are insufficient for clinical infection classification. Fingerprints-based omic analysis has attracted increasing attention globally for analyzing the complex host systemic immune response. A single type of fingerprints is not applicable for infection classification (area under curve (AUC) of 0.550-0.617). Herein, an infection classification platform based on deep learning of dual plasma fingerprints (DPFs-DL) is developed. The DPFs with high reproducibility (coefficient of variation <15%) are obtained at low sample consumption (550 nL native plasma) using inorganic nanoparticle and organic matrix assisted laser desorption/ionization mass spectrometry. A classifier (DPFs-DL) for viral versus bacterial infection discrimination (AUC of 0.775) and coronavirus disease 2019 (COVID-2019) diagnosis (AUC of 0.917) is also built. Furthermore, a metabolic biomarker panel of two differentially regulated metabolites, which may serve as potential biomarkers for COVID-19 management (AUC of 0.677-0.883), is constructed. This study will contribute to the development of precision clinical care for infectious diseases.

Clinical, Laboratory and Virological Characteristics of Patients with Positive Hepatitis B Surface Antigen

Background and Aim: Globally, Hepatitis B virus (HBV) infection is a major health issue contributing to various diseases such as hepatocellular carcinoma (HCC) and liver cirrhosis. Virus replication complex interaction with host immune system response causes dynamic interplay leading to HBV infection. In developing countries, HBV infection plays a significant role in higher rates of morbidities and mortalities. The present study aimed to assess the clinical, laboratory, and virological characteristics of patients with positive HBV surface antigen. Methodology: This cross-sectional study was carried out on 182 positive HBV surface antigen (HBsAg) in the department of Medicine, Social Security Hospital, Multan Road Lahore from April 2021 to March 2022. All the patients with positive HBsAg and negative hepatitis C were enrolled. Patients with a history of chronic liver disease, acute hepatitis B infection, and antiviral therapy were excluded. All patients underwent CBC, liver function tests, clinical evaluation, and abdominal ultrasonography examination, HBV serological marker’s assessment, HBV transmission risk factors, and HBV-DNA quantitative detection. SPSS version 25 was used for data analysis. Results: Out of 182 HBV infected patients, there were 162 (89%) males and 20 (11%) females. The overall mean age was 38.6 ± 8.6 years. The most prevalent complaint and common findings was arthralgia and hepatomegaly with reported incidence of 32 (17.6%) and 16 (8.8%) respectively. Based on ultrasonography imaging results, the incidence of normal liver, coarse liver, splenomegaly, and cirrhosis were found in 81.3% (n=148), 12.6% (n=23), 5.9% (n=11), and 6.6% (n=12) respectively. Based on laboratory results, normal alanine aminotransferase, normal aspartate aminotransferase, reduced serum albumin, and low platelet count were found in 76.9%, 84.8%, 4.9%, and 10.2% respectively. Regarding laboratory, clinical, and imaging characteristics, HBV-DNA positive and negative had no significant differences. Conclusion: The present study found that HBV infected patient’s clinical manifestations were fatigue, bleeding gums, abdominal pain and fatigue. Majority of patients had normal liver on liver function tests and ultrasonographic examination. Most patients had negative HBV infection antigen. Based on comparisons made between HBV-DNA negative and positive, no substantial variations were reported on laboratory, clinical, and imaging characteristics. Keywords: HBV antigen, Virological characteristics, HBV

Impact of Environmental Conditions on the Protein Content of Staphylococcus aureus and Its Derived Extracellular Vesicles.

Staphylococcus aureus, a major opportunistic pathogen in humans, produces extracellular vesicles (EVs) that are involved in cellular communication, the delivery of virulence factors, and modulation of the host immune system response. However, to date, the impact of culture conditions on the physicochemical and functional properties of S. aureus EVs is still largely unexplored. Here, we use a proteomic approach to provide a complete protein characterization of S. aureus HG003, a NCTC8325 derivative strain and its derived EVs under four growth conditions: early- and late-stationary growth phases, and in the absence and presence of a sub-inhibitory concentration of vancomycin. The HG003 EV protein composition in terms of subcellular localization, COG and KEGG categories, as well as their relative abundance are modulated by the environment and differs from that of whole-cell (WC). Moreover, the environmental conditions that were tested had a more pronounced impact on the EV protein composition when compared to the WC, supporting the existence of mechanisms for the selective packing of EV cargo. This study provides the first general picture of the impact of different growth conditions in the proteome of S. aureus EVs and its producing-cells and paves the way for future studies to understand better S. aureus EV production, composition, and roles.

The haustorium: The root of biotrophic fungal pathogens.

Biotrophic plant pathogenic fungi are among the dreadful pathogens that continuously threaten the production of economically important crops. The interaction of biotrophic fungal pathogens with their hosts necessitates the development of unique infection mechanisms and involvement of various virulence-associated components. Biotrophic plant pathogenic fungi have an exceptional lifestyle that supports nutrient acquisition from cells of a living host and are fully dependent on the host for successful completion of their life cycle. The haustorium, a specialized infection structure, is the key organ for biotrophic fungal pathogens. The haustorium is not only essential in the uptake of nutrients without killing the host, but also in the secretion and delivery of effectors into the host cells to manipulate host immune system and defense responses and reprogram the metabolic flow of the host. Although there is a number of unanswered questions in this area yet, results from various studies indicate that the haustorium is the root of biotrophic fungal pathogens. This review provides an overview of current knowledge of the haustorium, its structure, composition, and functions, which includes the most recent haustorial transcriptome studies.