Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation

Infectious diseases remain a major health problem and cause of death worldwide. It is expected that the socio-economic impact will further intensify due to escalating resistance to antibiotics, an ageing population and an increase in the number of patients under immunosuppressive therapy and implanted medical devices. Even though radiolabeled probes and leukocytes are routinely used in clinical practice, it might still be difficult to distinguish sterile inflammation from inflammation caused by bacteria. Moreover, the majority of these probes are based on the attraction of leukocytes which may be hampered in neutropenic patients. Novel approaches that can be implemented in clinical practice and allow for swift diagnosis of infection by targeting the microorganism directly, are posing an attractive strategy. Here we review the current strategies to directly image bacteria using radionuclides and we provide an overview of the preclinical efforts to develop and validate new approaches. Indeed, significant progress has been made in the past years, but very few radiopharmaceuticals (that were promising in preclinical studies) have made it into clinical practice. We will discuss the challenges that remain to select good candidates for imaging agents targeting bacteria.

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Do mitochondrial DNA mutations play the key role in chronification of sterile inflammation? Special focus on atherosclerosis

Current Pharmaceutical Design ◽

10.2174/1381612826666201012164330 ◽

2020 ◽

Vol 26 ◽

Author(s):

Alexander N. Orekhov ◽

Elena V. Gerasimova ◽

Vasily N. Sukhorukov ◽

Anastasia V. Poznyak ◽

Nikita G. Nikiforov

Keyword(s):

Innate Immunity ◽

Mitochondrial Dna ◽

Low Density Lipoprotein ◽

Atherosclerotic Lesion ◽

Density Lipoprotein ◽

Sterile Inflammation ◽

Special Focus ◽

Mitochondrial Dysfunctions ◽

Mtdna Mutations ◽

Dna Mutations

Background: The elucidation of mechanisms implicated in the chronification of inflammation is able to shed the light on the pathogenesis of disorders that are responsible for the majority of the incidence of disease and deaths, and also causes of ageing. Atherosclerosis is an example of the most significant inflammatory pathology. The inflammatory response of innate immunity is implicated in the development of atherosclerosis arising locally or focally. Modified low-density lipoprotein (LDL) was regarded as the trigger for this response. No atherosclerotic changes in the arterial wall occur due to the quick decrease in inflammation rate. Nonetheless, the atherosclerotic lesion formation can be a result of the chronification of local inflammation, which, in turn, is caused by alteration of the response of innate immunity. Objective: In this review, we discussed potential mechanisms of the altered response of the immunity in atherosclerosis with a particular emphasis on mitochondrial dysfunctions. Conclusion: A few mitochondrial dysfunctions can be caused by the mitochondrial DNA (mtDNA) mutations. Moreover, mtDNA mutations were found to affect the development of defective mitophagy. Modern investigations have demonstrated the controlling mitophagy function in the response of the immune system. Therefore, we hypothesized that impaired mitophagy, as a consequence of mutations in mtDNA, can raise a disturbed innate immunity response resulting in the chronification of inflammation in atherosclerosis.

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