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Nature Sep 2021Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells. There are several inflammasome sensors that...
Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells. There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively). During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors. Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 and Francisella novicida. We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1 that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases.
Topics: Animals; Apoptosis; Caspase 1; Cells, Cultured; Cytokines; DNA-Binding Proteins; Female; Francisella; Herpesvirus 1, Human; Humans; Male; Mice; Mice, Inbred C57BL; Necroptosis; Pyrin; Pyroptosis; RNA-Binding Proteins; THP-1 Cells
PubMed: 34471287
DOI: 10.1038/s41586-021-03875-8 -
Microorganisms Oct 2021Immune responses to intracellular pathogens depend largely upon the activation of T helper type 1-dependent mechanisms. The contribution of B cells to establishing... (Review)
Review
Immune responses to intracellular pathogens depend largely upon the activation of T helper type 1-dependent mechanisms. The contribution of B cells to establishing protective immunity has long been underestimated. , including a number of subspecies, provides a suitable model for the study of immune responses against intracellular bacterial pathogens. We previously demonstrated that infects B cells and activates B-cell subtypes to produce a number of cytokines and express the activation markers. Recently, we documented the early production of natural antibodies as a consequence of infection in mice. Here, we summarize current knowledge on the innate and acquired humoral immune responses initiated by infection and their relationships with the immune defense systems.
PubMed: 34683457
DOI: 10.3390/microorganisms9102136 -
Tidsskrift For Den Norske Laegeforening... Aug 2021The diagnosis of pulmonary tularaemia can be challenging. We present a case illustrating how pulmonary tularaemia may be an important radiological differential diagnosis...
BACKGROUND
The diagnosis of pulmonary tularaemia can be challenging. We present a case illustrating how pulmonary tularaemia may be an important radiological differential diagnosis to lung cancer.
CASE PRESENTATION
A man in his fifties presented with several weeks of dry cough, weight loss and profuse night sweats. The physical examination was normal. A chest computer tomography showed evidence of lymphadenopathy and two consolidated lung masses. The lung masses and lymph nodes showed signs of necrosis. The radiological findings were described as suspicious of lung cancer. A detailed history revealed that he had chopped wood prior to symptom onset. He tested positive for Francisella tularensis IgM and IgG, confirming the diagnosis of pulmonary tularaemia.
INTERPRETATION
The radiological findings in pulmonary tularaemia may mimic lung cancer. Serology is an easy way to confirm the diagnosis, if faced with clinical or radiological suspicion of pulmonary tularaemia.
Topics: Antibodies, Bacterial; Cough; Diagnosis, Differential; Francisella tularensis; Humans; Lung Neoplasms; Male; Tularemia
PubMed: 34423953
DOI: 10.4045/tidsskr.21.0245 -
Virulence Dec 2023Tularaemia is a zoonotic disease caused by the Gram-negative bacterium, . Depending on its entry route into the organism, causes different diseases, ranging from... (Review)
Review
Tularaemia is a zoonotic disease caused by the Gram-negative bacterium, . Depending on its entry route into the organism, causes different diseases, ranging from life-threatening pneumonia to less severe ulceroglandular tularaemia. Various strains with different geographical distributions exhibit different levels of virulence. is an intracellular bacterium that replicates primarily in the cytosol of the phagocytes. The main virulence attribute of is the type 6 secretion system (T6SS) and its effectors that promote escape from the phagosome. In addition, has evolved a peculiar envelope that allows it to escape detection by the immune system. In this review, we cover tularaemia, different strains, and their pathogenicity. We particularly emphasize the intracellular life cycle, associated virulence factors, and metabolic adaptations. Finally, we present how largely escapes immune detection to be one of the most infectious and lethal bacterial pathogens.
Topics: Humans; Francisella tularensis; Virulence; Tularemia; Virulence Factors; Phagosomes
PubMed: 37941380
DOI: 10.1080/21505594.2023.2274638 -
Annual Review of Entomology Jan 2020Tularemia is a Holarctic zoonosis caused by the gamma proteobacterium and is considered to be a vector-borne disease. In many regions, human risk is associated with the... (Review)
Review
Tularemia is a Holarctic zoonosis caused by the gamma proteobacterium and is considered to be a vector-borne disease. In many regions, human risk is associated with the bites of flies, mosquitoes, or ticks. But the biology of the agent is such that risk may be fomite related, and large outbreaks can occur due to inhalation or ingestion of contaminated materials. Such well-documented human risk factors suggest a role for these risk factors in the enzootic cycle as well. Many arthropods support the growth or survival of the agent, but whether arthropods (ticks in particular) are obligately required for the perpetuation of remains to be demonstrated. As with most zoonoses, our knowledge of the ecology of has been driven with the objective of understanding human risk. In this review, we focus on the role of the arthropod in maintaining , particularly with respect to long-term enzootic persistence.
Topics: Animals; Arthropod Vectors; Biological Evolution; Francisella tularensis; Tularemia
PubMed: 31600457
DOI: 10.1146/annurev-ento-011019-025134 -
Microorganisms Dec 2020(Ft) is the etiological agent of tularemia, a disease known for over 100 years in the northern hemisphere. Ft includes four subspecies, of which two are the etiologic... (Review)
Review
(Ft) is the etiological agent of tularemia, a disease known for over 100 years in the northern hemisphere. Ft includes four subspecies, of which two are the etiologic agents of tularemia: Ft subsp. (Ftt) and Ft subsp. (Fth), mainly distributed in North America and the whole northern hemisphere, respectively. Several routes of human infection with these bacteria exist, notably through bites of Ixodidae ticks. However, mosquitoes represent the main vectors of Fth in Scandinavia, where large tularemia outbreaks have occurred, usually during the warm season. The mechanisms making mosquitoes vectors of Fth are still unclear. This review covers the inventory of research work and epidemiological data linking tularemia to mosquitoes in Scandinavia and highlights the gaps in understanding mosquitoes and Ft interactions.
PubMed: 33374861
DOI: 10.3390/microorganisms9010026 -
Frontiers in Cellular and Infection... 2020Tularemia is a zoonotic disease caused by the bacterium . The predominant sources, routes of infection, and clinical manifestations of human infections greatly vary... (Review)
Review
Tularemia is a zoonotic disease caused by the bacterium . The predominant sources, routes of infection, and clinical manifestations of human infections greatly vary according to the geographic area considered. Moreover, clinical suspicion of tularemia is often tricky because of the lack of specificity of the clinical manifestations. Because isolation is tedious and detection of its DNA usually requires removal of infected tissues, serological techniques are most often used for diagnostic confirmation. However, these techniques are varied and poorly standardized. The microagglutination test (MAT), the indirect immunofluorescence assay (IFA), and ELISA tests are currently the most frequently used techniques. These home-made and commercial tests are mainly used for tularemia diagnosis but also seroprevalence studies. ELISA tests detect specific antibodies within two weeks of disease evaluation, compared to 2-3 weeks for MAT and IFA. However, more false-positive results are usually reported with ELISA. The long-term persistence of anti- antibodies in patients with past tularemia infection hampers the diagnostic specificity of all these tests. Also, cross-reacting antibodies have been described (especially with and species), although usually at a low level. The immunoblotting technique can highlight these serological cross-reactions. Tularemia remains an underdiagnosed disease in most endemic areas, and the clinical presentations of this disease are evolving. It is necessary to improve further speed and accuracy of tularemia diagnosis, as well as the standardization of diagnostic procedures.
Topics: Adolescent; Adult; Animals; Antibodies, Bacterial; Child; Female; Francisella tularensis; Humans; Male; Middle Aged; Seroepidemiologic Studies; Tularemia; Young Adult; Zoonoses
PubMed: 33194778
DOI: 10.3389/fcimb.2020.512090 -
Annals of Agricultural and... Mar 2022Tularaemia is an infrequently occurring disease in Poland. It has therefore rarely been taken into account in the differential diagnosis of skin lesions, lymphadenitis,... (Review)
Review
INTRODUCTION AND OBJECTIVE
Tularaemia is an infrequently occurring disease in Poland. It has therefore rarely been taken into account in the differential diagnosis of skin lesions, lymphadenitis, or soft tissue abscesses. This fact, accompanied by non-specific initial presentation, may lead to a delay in diagnosis and a more severe course of the disease. Objective. The aim of the study is to present the current state of knowledge on tularaemia and convince medical professionals to take it into consideration in the diagnosis of skin lesions, lymphadenitis, and tissue abscesses.
REVIEW METHODS
A literature review using PubMed and other online resources, using terms including 'tularaemia', 'lymphadenitis', etc., was undertaken. Papers were reviewed for relevance and scientific merit.
ABBREVIATED DESCRIPTION OF THE STATE OF KNOWLEDGE
Tularaemia, also known as 'rabbit fever', is a zoonotic infection caused by Francisella tularensis, an aerobic, facultative intracellular, gram-negative bacteria. In Europe, it is mainly spread via tick bites and contact with wild animals such as lagomorphs and rodents. Clinical presentation may differ depending on the transmission route; the ulceroglandular and glandular forms of disease predominate. An early diagnosis and implementation of appropriate antibiotic therapy are the cornerstones of successful treatment and make it possible to avoid a surgical incision and drainage of suppurative complications.
SUMMARY
Raised awareness and knowledge on tularaemia among health care professionals are required for timely diagnosis and treatment. Arrival from endemic areas, contact with wild animals, tick bites, and exclusion of more common etiologies of presenting signs should prompt consideration of tularaemia. More research is needed for a better understanding of the burden of the disease and its impact on public health in Poland.
Topics: Animals; Anti-Bacterial Agents; Europe; Francisella tularensis; Rabbits; Tularemia; Zoonoses
PubMed: 35352900
DOI: 10.26444/aaem/139242