Powerful Defense Research Articles

IMMU-48. CD4+ T CELLS RESTRICT MEDULLOBLASTOMA GROWTH AND DISSEMINATION

Abstract The immune system serves as a powerful defense not only against pathogens and parasites but also against neoplastic cells. Emerging immunotherapies that boost the activity of tumor-reactive immune cells or counteract immune suppressive mechanisms have shown promising effects in certain types of cancer. However, the success of immunotherapy for brain tumors has been limited, highlighting the need for a better understanding of the immune microenvironment in these tumors. Our previous studies have shown that T cells critically affect growth of the pediatric brain tumor medulloblastoma. In particular, depletion of CD4+ T cells results in more aggressive growth of medulloblastoma cells and allows these cells to metastasize to the spinal cord. The anti-tumoral effects of CD4+ T cells are not due to their function as helpers for CD8+ cytotoxic T cells, since CD8+ T cell depletion did not enhance tumor growth to the same extent as CD4+ T cell depletion. To test whether CD4+ T cells can recognize MHC class II molecules on tumor cells and attack these cells directly, we generated tumors from MHC class II knockout mice. Surprisingly, depletion of CD4+ cells in these animals still enhanced tumor growth and metastasis. These results suggest that CD4+ T cells regulate medulloblastoma growth and metastasis in a manner that is independent of CD8+ T cells and independent of MHC-II on tumor cells. Ongoing studies are aimed at elucidating the mechanisms by which CD4+ T cells regulate medulloblastoma growth, including the antigen-presenting cells that activate them and the effector cells responsible for killing tumor cells following their activation. These studies will advance our understanding of the immune microenvironment in medulloblastoma and allow us to design more effective therapies for controlling tumor growth and metastasis.

P.832DRD1 protein and mRNA levels in peripheral blood lymphocytes: influence of SNPs of 5′-untranslated region and the schizophrenia disorder

Apoptosis is a powerful host cell defense to prevent viruses from completing replication. Poxviruses have evolved complex means to dampen cellular apoptotic responses. The poxvirus, Molluscum Contagiosum Virus (MCV), encodes numerous host interacting molecules predicted to antagonize immune responses. However, the function of the majority of these MCV products has not been characterized. Here, we show that the MCV MC163 protein localized to the mitochondria via an N-terminal mitochondrial localization sequence and transmembrane domain. Transient expression of the MC163 protein prevented mitochondrial membrane permeabilization (MMP), an event central to cellular apoptotic responses, induced by either Tumor Necrosis Factor alpha (TNF-α) or carbonyl cyanide 3-chlorophenylhydrazone (CCCP). MC163 expression prevented the release of a mitochondrial intermembrane space reporter protein when cells were challenged with TNF-α. Inhibition of MMP was also observed in cell lines stably expressing MC163. MC163 expression may contribute to the persistence of MCV lesions by dampening cellular apoptotic responses.

Citizens Without Robes: On the Deliberative Potential of Everyday Politics

This essay is a sympathetic critical comment on Cristina Lafont’s recent book, Democracy without Shortcuts: A Participatory Conception of Deliberative Democracy. I focus primarily on the arguments in the final chapters of the book that introduce a deliberative democratic re-interpretation of judicial review. Lafont appeals to the evocative imagery of citizens in robes and suggests that contesting legislation at the level of the supreme court does not take questions out of the public sphere and into the legal domain but rather brings questions of right and constitutionality into the political domain. The institutional possibility for individual citizens to challenge any law and thus launch a broad public debate that demands justifications and reasons is the heart of Lafont’s conception of participatory deliberative democracy. I find this a powerful and compelling defense and understanding of judicial review. I question, however, what appears to be a narrowing of deliberative democracy to constitutional contestation and so an abandonment of everyday politics where issues, debates, and controversies are not structured by the constraint of constitutional discourse. I argue that the focus on constitutional politics, made necessarily by her public reason requirement, narrows the range of her theory and appears to leave everyday politics outside the scope of deliberative democracy.

Nrf2 in Neoplastic and Non-Neoplastic Liver Diseases.

Simple SummaryAlthough the Keap1-Nrf2 pathway represents a powerful cell defense mechanism against a variety of toxic insults, its role in acute or chronic liver damage and tumor development is not completely understood. This review addresses how Nrf2 is involved in liver pathophysiology and critically discusses the contrasting results emerging from the literature. The aim of the present report is to stimulate further investigation on the role of Nrf2 that could lead to define the best strategies to therapeutically target this pathway.Activation of the Keap1/Nrf2 pathway, the most important cell defense signal, triggered to neutralize the harmful effects of electrophilic and oxidative stress, plays a crucial role in cell survival. Therefore, its ability to attenuate acute and chronic liver damage, where oxidative stress represents the key player, is not surprising. On the other hand, while Nrf2 promotes proliferation in cancer cells, its role in non-neoplastic hepatocytes is a matter of debate. Another topic of uncertainty concerns the nature of the mechanisms of Nrf2 activation in hepatocarcinogenesis. Indeed, it remains unclear what is the main mechanism behind the sustained activation of the Keap1/Nrf2 pathway in hepatocarcinogenesis. This raises doubts about the best strategies to therapeutically target this pathway. In this review, we will analyze and discuss our present knowledge concerning the role of Nrf2 in hepatic physiology and pathology, including hepatocellular carcinoma. In particular, we will critically examine and discuss some findings originating from animal models that raise questions that still need to be adequately answered.

Justice & its motives: On Peter Vanderschraaf’sStrategic Justice

Peter Vanderschraaf’s Strategic Justice is a powerful elaboration and defense of what he calls ‘justice as mutual advantage’. Vanderschraaf opens Strategic Justice by observing that ‘Plato set a template for all future philosophers by raising two interrelated questions: (1) What precisely is justice? (2) Why should one be just?’. He answers that (1) justice consists of conventions which (2) are followed because each sees that doing so is in her interest. These answers depend upon two conditions which Vanderschraaf calls Baseline Consistency and Negative Mutual Expectations. I contend that the plausibility of the first condition depends upon principles which are prior to Vanderchraaf’s conventions of justice and that the second condition does not account for the interest Vanderschraaf must think we take in those principles. I therefore worry that Vanderschraaf does what he accuses other theorists of justice as mutual advantage of doing: going outside the bounds of justice as mutual advantage. To lay the groundwork for his conditions, Vanderschraaf analyzes the circumstances of justice. I argue that, his claims to the contrary notwithstanding, he does not take the circumstances to be the kind of conditions Hume takes them to be, but that he has good reason to do so.

The Defence of Aachaaram, Femininity, and Neo-Savarna Power in Kerala

This paper examines the discourse of the Ready to Wait (RTW) campaign, led by highly-educated professional neo-savarna women in Kerala, against litigation to open the doors of Kerala’s Sabarimala shrine to women of menstruating ages, hitherto barred from the pilgrimage. The term savarna refers to the privileged caste-communities that, from pre-colonial times, controlled land and other material resources and ritual practices, and continued to do so to a large extent even later. Avarna refers to those oppressed groups that laboured for the savarna and were subjected to degradation through such practices as untouchability and unseeability, and whose exclusion from social power continues in different ways despite these groups having achieved economic presence and education. Following a Supreme Court verdict in September 2018, which struck down the Sabarimala taboo, Kerala was shaken by violent protests led by neo-savarna and SanghParivar organisations. Through a close reading of the Facebook engagement of a Right to Wait campaigner, I seek to make sense of the particular sorts of ‘dissonance’ these organisations seem to be creating within the male-defined space of Hindutva, the specific caste politics they represent, as well as their articulation and disarticulation with a discourse on women’s empowerment and feminism. I argue that it is time that we seriously theorise the power relations between the savarna and avarna women under brahminical patriarchy, instead of focusing singularly on the subordination of upper-caste women by the male brahminical elite.

Bias Busters: Robustifying DL-Based Lithographic Hotspot Detectors Against Backdooring Attacks

Deep learning (DL) offers potential improvements throughout the CAD tool-flow, one promising application being lithographic hotspot detection. However, DL techniques have been shown to be especially vulnerable to inference and training time adversarial attacks. Recent work has demonstrated that a small fraction of malicious physical designers can stealthily “backdoor” a DL-based hotspot detector during its training phase such that it accurately classifies regular layout clips but predicts hotspots containing a specially crafted trigger shape as nonhotspots. We propose a novel training data augmentation strategy as a powerful defense against such backdooring attacks. The defense works by eliminating the intentional biases introduced in the training data but does not require knowledge of which training samples are poisoned or the nature of the backdoor trigger. Our results show that the defense can drastically reduce the attack success rate from 84% to ~0%.

DNA unchained: two assays to discover and study inhibitors of the DNA clustering function of barrier-to-autointegration factor

The protein barrier-to-autointegration factor (BAF) and its interaction partners, the LEM (LAP2B, emerin, MAN1)-domain proteins, constitute a powerful cytoplasmic DNA defense mechanism. Invading DNA molecules are quickly bound by the BAF system and trapped in membrane compartments. This decreases the nuclear uptake of DNA from the cytoplasm. Inhibition of the BAF system is therefore expected to enhance the efficacy of non-viral DNA transfection agents. In this study, we introduced a protocol for the recombinant expression of soluble BAF and developed two ELISA-type assays to discover small molecule inhibitors of BAF-dependent DNA retention by high throughput screening (HTS). The proton pump inhibitor rabeprazole as well as three compounds of the Maybridge library were identified as inhibitors of the LEM-BAF-DNA interaction chain. The inhibition was based on adduct formation with BAF cysteine residues. An enhancing effect of the compounds on cell culture transfection, however, was not observed, which may be attributed to the reducing environment of the cytoplasm that prevents the adduct formation with BAF cysteine residues. The novel assays developed here can provide new tools to further study the biological functions of the BAF system, and may lead to the identification of suitable BAF inhibitors in future HTS campaigns.

Senescence and Host-Pathogen Interactions.

Damage to our genomes triggers cellular senescence characterised by stable cell cycle arrest and a pro-inflammatory secretome that prevents the unrestricted growth of cells with pathological potential. In this way, senescence can be considered a powerful innate defence against cancer and viral infection. However, damage accumulated during ageing increases the number of senescent cells and this contributes to the chronic inflammation and deregulation of the immune function, which increases susceptibility to infectious disease in ageing organisms. Bacterial and viral pathogens are masters of exploiting weak points to establish infection and cause devastating diseases. This review considers the emerging importance of senescence in the host–pathogen interaction: we discuss the pathogen exploitation of ageing cells and senescence as a novel hijack target of bacterial pathogens that deploys senescence-inducing toxins to promote infection. The persistent induction of senescence by pathogens, mediated directly through virulence determinants or indirectly through inflammation and chronic infection, also contributes to age-related pathologies such as cancer. This review highlights the dichotomous role of senescence in infection: an innate defence that is exploited by pathogens to cause disease.

EIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition.

RNA-activated protein kinase (PKR) is a major innate immune factor that senses viral double-stranded RNA (dsRNA) and phosphorylates eukaryotic initiation factor (eIF) 2α. Phosphorylation of the α subunit converts the eIF2αβγ complex into a stoichiometric inhibitor of eukaryotic initiation factor eIF2B, thus halting mRNA translation. To escape this protein synthesis shutoff, viruses have evolved countermechanisms such as dsRNA sequestration, eIF-independent translation by an internal ribosome binding site, degradation of PKR, or dephosphorylation of PKR or of phospho-eIF2α. Here, we report that sandfly fever Sicilian phlebovirus (SFSV) confers such a resistance without interfering with PKR activation or eIF2α phosphorylation. Rather, SFSV expresses a nonstructural protein termed NSs that strongly binds to eIF2B. Although NSs still allows phospho-eIF2α binding to eIF2B, protein synthesis and virus replication are unhindered. Hence, SFSV encodes a unique PKR antagonist that acts by rendering eIF2B resistant to the inhibitory action of bound phospho-eIF2α.IMPORTANCE RNA-activated protein kinase (PKR) is one of the most powerful antiviral defense factors of the mammalian host. PKR acts by phosphorylating mRNA translation initiation factor eIF2α, thereby converting it from a cofactor to an inhibitor of mRNA translation that strongly binds to initiation factor eIF2B. To sustain synthesis of their proteins, viruses are known to counteract this on the level of PKR or eIF2α or by circumventing initiation factor-dependent translation altogether. Here, we report a different PKR escape strategy executed by sandfly fever Sicilian virus (SFSV), a member of the increasingly important group of phleboviruses. We found that the nonstructural protein NSs of SFSV binds to eIF2B and protects it from inactivation by PKR-generated phospho-eIF2α. Protein synthesis is hence maintained and the virus can replicate despite ongoing full-fledged PKR signaling in the infected cells. Thus, SFSV has evolved a unique strategy to escape the powerful antiviral PKR.

War and negotiations. How Vietnam defeated the American Colossus

Over the course of the prolonged US war in Vietnam, the bloodiest one after World War II, it became obvious that there was no alternative to a negotiation process. Important reasons were the impossibility for Washington to win the battlefield and the rise of anti-war sentiment in the United States. The author tried to show how certain psychological characteristics of US leaders led to the war and then eventually to negotiations. When started negotiations were accompanied by military action. The course of the war and negotiations was influenced by Soviet military assistance to the DRV, as well as by relations in the triangle of the USSR - USA - China. The time of detente between the USSR and the USA coincided with war in Vietnam, which influenced the behavior of the Soviet leaders, as evidenced by the recollections of the USSR ambassador to the United States A. Dobrynin.The Politburo of the Central Committee had disagreements regarding Vietnam and detente with the United States. But the war weakened US international stance and contributed to the achievement of strategic agreements with the USSR.The main objectives of the DRV in the negotiations were to stop US bombings and then withdrawal of US troops. The United States sought to maintain the Saigon puppet regime for some time after the withdrawal of its troops from South Vietnam. Washington’s main goal was to “save its face”, declaring defeat a “victory”. To achieve this goal the war and negotiations dragged on for years, and on the eve of the signing of the agreements, the most fierce bombing of the DRV was carried out.Thanks to the powerful air defense created with the help of the USSR, the DRV won the “air Dien Bien Fu”.The United States was forced to sign a peace agreement, which provided for the complete cessation of all US military operations in Vietnam, the withdrawal of all American troops, but left the North Vietnamese forces in South Vietnam together with the armed forces of the National Liberation Front along with the decaying and doomed to death Saigon regime. In 1975 its army was defeated the regime capitulated, which ensured the subsequent reunification of South and North Vietnam.The Vietnamese people defeated the American colossus, having suffered terrible sacrifices themselves, but achieved the national goal - the withdrawal of the Americans and the unification of the country. The full support of Vietnam can be seen as a successes story of Soviet foreign policy.

Induction and Evasion of Type-I Interferon Responses during Influenza A Virus Infection.

Influenza A viruses (IAVs) are contagious pathogens and one of the leading causes of respiratory tract infections in both humans and animals worldwide. Upon infection, the innate immune system provides the first line of defense to neutralize or limit the replication of invading pathogens, creating a fast and broad response that brings the cells into an alerted state through the secretion of cytokines and the induction of the interferon (IFN) pathway. At the same time, IAVs have developed a plethora of immune evasion mechanisms in order to avoid or circumvent the host antiviral response, promoting viral replication. Herein, we will review and summarize already known and recently described innate immune mechanisms that host cells use to fight IAV viral infections as well as the main strategies developed by IAVs to overcome such powerful defenses during this fascinating virus-host interplay.

Падіння Берлінського муру та сучасні виклики спорудження нових стін: рефлексія BASEES

The conference of the British Association of Slavic and Eastern European Studies (BASEES) in 2019 was dedicated to the 30th anniversary of the fall of the Berlin Wall, the event that marked democracy triumph and liberation of communist authoritarianism. The focus was made on the factors of this victory, in particular on the role played in it by intellectuals of that time. The problem of scholars’ public activity was brought to the forefront by the thesis that achievements of science and education are not only theoretical developments and their successful assimilation in the form of knowledge, but also the level of influence science and education have in the society. Transition from instrumental rationality to rationality of values enhances practical importance of intellectual activity. Addressing this issue is particularly important in the context of crisis in the values ​​of liberal democracy and increasing distrust of rational knowledge and culture. Modern technologies of manipulating consciousness contribute to the strengthening of authoritarian regimes. Therefore, the experience of intellectuals under communist authoritarianism must teach contemporary scholars to uphold the values ​​of freedom and democracy and maintain social optimism. The discussion on the fall of the Berlin Wall proved that the scholars’ civic and academic positions reinforce each other, thereby forming a powerful defence against authoritarianism. However, the reincarnation of authoritarian sentiment nowadays provides grounds for accusing intellectuals of their inability to face up the challenges of the present. Among those challenges, we should mention forgetting the horribleness of old walls and illusions on benefits of constructing new ones.

Host Directed Therapy Against Infection by Boosting Innate Immunity.

The innate immune system constitutes the first line of defense against invading pathogens, regulating the normal microbiota and contributes to homeostasis. Today we have obtained detailed knowledge on receptors, signaling pathways, and effector molecules of innate immunity. Our research constellation has focused on ways to induce the expression of antimicrobial peptides (AMPs), the production of oxygen species (ROS and NO), and to activate autophagy, during the last two decades. These innate effectors, with different mechanisms of action, constitute a powerful defense armament in phagocytes and in epithelial cells. Innate immunity does not only protect the host from invading pathogens, but also regulates the composition of the microbiota, which is an area of intense research. Notably, some virulent bacteria have the capacity to downregulate innate defenses and can thereby cause invasive disease. Understanding the detailed mechanisms behind pathogen-mediated suppression of innate effectors are currently in progress. This information can be of importance for the development of novel treatments based on counteraction of the downregulation; we have designated this type of treatment as host directed therapy (HDT). The concept to boost innate immunity may be particularly relevant as many pathogens are developing resistance against classical antibiotics. Many pathogens that are resistant to antibiotics are sensitive to the endogenous effectors included in early host defenses, which contain multiple effectors working in cooperation to control infections. Here, we review recent data related to downregulation of AMPs by pathogenic bacteria, induction of innate effector mechanisms, including cytokine-mediated effects, repurposed drugs and the role of antibiotics as direct modulators of host responses. These findings can form a platform for the development of novel treatment strategies against infection and/or inflammation.

Countering Counter-Defense to Antiviral RNAi.

RNA interference (RNAi) is a powerful host defense mechanism against viruses. As a counter-defense, many viruses encode suppressors of RNAi, which - in plants - has provoked counter-counter-defense strategies. Recently, a mechanism was proposed in Drosophila (Zhang et al.) wherein a long noncoding RNA senses a virus-encoded RNAi suppressor to activate an innate immune response.

Profiles of Immune Infiltration and Prognostic Immunoscore in Lung Adenocarcinoma.

Lung tissue is abundant with immune cells that form a powerful first defense against exotic particles and microbes. The malignant phenotype of lung adenocarcinoma (LUAD) is defined not only by intrinsic tumor cells but also by tumor-infiltrating immune cells (TIICs) recruited to the immune microenvironment. Understanding more about the immune microenvironment of LUAD could function in sorting out patients more likely with high risk and benefit from immunotherapy. Twenty-two types of TIICs were estimated based on large public LUAD cohorts from the TCGA and GEO datasets using the CIBERSORT algorithm. Then principal component analysis (PCA), meta-analysis, and single-sample gene set enrichment analysis (ssGSEA) were used to measure and evaluate the specific immune responses and relative mechanisms. Moreover, an immunoscore model based on the percent of immune cells was constructed via the univariate and multivariate Cox regression models, which provided an in-depth overview of the LUAD immune microenvironment and shed light on the immune regulatory mechanism. The differential expression genes (DEGs) were acquired based on the immunoscore model, and prognostic immune-related genes were further identified. GSEA and the protein–protein interaction network (PPI) further revealed that these genes were mostly enriched in many immune-related biological processes. It is hoped that this immune landscape could provide a more accurate understanding for LUAD development and tumor immune therapy.

1148-P: Antioxidative Effects of Empagliflozin and Metformin in Type 1 Diabetes Mellitus Patients

Background: Favourable cardiovascular effects of SGLT2 inhibitors have been clearly revealed, whereas the underlying mechanism(s) still remain unknown. We explored the anti-oxidative action of empagliflozin (alone and in combination with metformin) in type 1 diabetes mellitus (T1DM) patients. Methods: Forty T1DM male patients (age 44.7 ± 2.5 years, BMI 28.3 ± 0.6 kg/m2) were equally randomised into four groups: 1) control (placebo), 2) empagliflozin (25 mg daily), 3) metformin (2000 mg daily) and 4) combination (empagliflozin 25 mg daily and metformin 2000 mg daily). Oxidative stress parameters were assessed at inclusion and after 12 weeks of treatment, comprising of total antioxidative status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), isoprostane, interleukin 6 (IL6) and advanced oxidation protein products (AOPP). One-way analysis of variance (ANOVA) with Bonferroni post-test was used for statistical analysis. Results: Empagliflozin in combination with metformin significantly improved antioxidative status parameters by increasing TAS for up to 1.07-fold (P<0.01), SOD for up to 1.08-fold (P<0.001) and GPx for up to 1.15-fold (P<0.01), whereas empagliflozin or metformin alone were less effective. The prooxidants significantly decreased in groups treated with empagliflozin alone or empagliflozin in combination with metformin: isoprostane for up to 1.26-fold (P<0.001) and IL6 for up to 1.34-fold (P<0.01); whereas the level of AOPP significantly decreased only in the group treated with empagliflozin and metformin combination (for up to 1.22-fold; P<0.01). The levels of oxidative stress parameters in the control group remained unchanged. Conclusion: We found that empagliflozin in combination with metformin provided powerful antioxidative defense in T1DM patients. The results could at least partially explain the beneficial effects of the two drugs beyond glucose control. Antioxidant activity should be focused on in further large clinical studies. Disclosure M. Janic: None. M. Lunder: None. M. Sabovic: None. A. Janez: None.

Investigating and Presenting an Alibi Defense

The New Jersey Supreme Court has said that “few defenses have greater potential for creating reasonable doubt as to a defendant's guilt in the minds of the [jurors than an alibi].” But is alibi a powerful defense, or a risky gambit with a high likelihood of backfiring? In two-thirds of exoneration cases, the innocent defendant offered an alibi which was rejected by the fact finder. This article explores the psychology of autobiographical memory, how police and jurors perceive alibi witnesses, common interview and interrogation tactics, common cross-examination questions, and offers some guidance about how to better present this defense.

Investigating and Presenting an Alibi Defense

The New Jersey Supreme Court has said that “few defenses have greater potential for creating reasonable doubt as to a defendant's guilt in the minds of the [jurors than an alibi].” But is alibi a powerful defense, or a risky gambit with a high likelihood of backfiring? In two-thirds of exoneration cases, the innocent defendant offered an alibi defense at trial which was rejected by the fact-finder. This article talks about alibi defenses from psychological research into the defendant's autobiographical memory and investigator tactics in the interrogation room, to alibi witnesses' memory and susceptibility to post-event information, to expected cross-examination and other courtroom issues.

Innate immune receptors in development of Mycobacterium tuberculosis infection

According to the World Health Organization, over 10 million new tuberculosis cases are reported annually worldwide. According to the 2017 Federal State Statistics Service Report, incidence rate for active TB infection in the Russian Federation was 109.8 cases per 100,000 population, of which 41.3% accounted for chronic disease form. Regardless of climatic conditions, high prevalence of TB infection, is not only due to high Mycobacterium tuberculosis viability, but also its ability for long persistence in human body and reactivation after an unlimited period of dormancy. The outcome of infection is largely determined by host immunoreactivity and its ability to develop protective immune response. In addition, status of immune system also underlies tuberculosis course after the onset: either as a localized form, or as a form with extensive damage to the lungs and even other organs observed in generalized infection. In recent decades, a great attention was paid to examining mechanisms of adaptive cell immunity played in pathogenesis of TB infection. No doubt, adaptive immunity is a powerful defense system providing a targeted specific immune response, but now it is becoming clear that it represents solely an effector arm of innate immunity. Innate immunity is a phylogenetically more ancient, inherited system largely aimed at ensuring rapid pathogen elimination and preventing development of infection at early stages when adaptive immunity ongoing antigen-specific maturation. Mechanisms of innate immunity mediated by cells, diverse receptors, molecules and their complexes, found on various cells. Activation of innate immunity begins with recognition of conserved molecular groups present in various pathogens called pathogen-associated molecular patterns (PAMPs), which are sensed by pathogen recognition receptors (PRRs). Here, we review current data on the role of innate receptors in recognizing M. tuberculosis-derived PAMPs, production of immunoregulatory cytokines and activation of signaling pathways playing a crucial role in the regulation of necroptosis, apoptosis and autophagy of infected macrophages. Significance of innate mucosal factors in implementing immune response to M. tuberculosis is discussed. In particular, Toll-like receptors, scavenger-receptors, mannose receptor, DC-SIGN etc. were described to participate in development of M. tuberculosis immunity. The data on single nucleotide polymorphic variants for innate genes are shown, which predispose to developing tuberculosis and affecting its course.