Converging studies have shown that M1 and M2 macrophages are functionally polarized in response to microorganisms and host mediators. Gene expression profiling of macrophages reveals that various Gram-negative and Gram-positive bacteria induce the transcriptional activity of a “common host response,” which includes genes belonging to the M1 program. However, excessive or prolonged M1 polarization can lead to tissue injury and contribute to pathogenesis. The so-called M2 macrophages play a critical role in the resolution of inflammation by producing anti-inflammatory mediators. These M2 cells cover a continuum of cells with different phenotypic and functional properties. In addition, some bacterial pathogens induce specific M2 programs in macrophages. In this review, we discuss the relevance of macrophage polarization in three domains of infectious diseases: resistance to infection, infectious pathogenesis, and chronic evolution of infectious diseases.
Potentially pathogenic bacteria, such as Escherichia coli and Vibrio cholerae, become non-culturable during stasis. The analysis of such cells has been hampered by difficulties in studying bacterial population heterogeneity. Using in situ detection of protein oxidation in single E. coli cells, and using a density-gradient centrifugation technique to separate culturable and non-culturable cells, we show that the proteins in non-culturable cells show increased and irreversible oxidative damage, which affects various bacterial compartments and proteins. The levels of expression of specific stress regulons are higher in non-culturable cells, confirming increased defects relating to oxidative damage and the occurrence of aberrant, such as by amino-acid misincorporation, proteins. Our data suggest that non-culturable cells are produced due to stochastic deterioration, rather than an adaptive programme, and pinpoint oxidation management as the 'Achilles heel' of these cells.
Background Covid-19 clinical expression is pleiomorphic, severity is related to age and comorbidities such as diabetes and hypertension, and pathophysiology involves aberrant immune activation and lymphopenia. We wondered if the myeloid compartment was affected during Covid-19 and if monocytes and macrophages could be infected by SARS-CoV-2. Methods Monocytes and monocyte-derived macrophages from Covid-19 patients and controls were infected with SARS-CoV-2, and extensively investigated with immunofluorescence, viral RNA extraction and quantification, total RNA extraction followed by reverse transcription and q-PCR using specific primers, supernatant cytokines (IL-10, TNF-α, IL-1β, IFN-β, TGF-β1 and IL-6), flow cytometry. The effect of M1- versus M2-type or no polarization prior to infection was assessed. Results SARS-CoV-2 efficiently infected monocytes and MDMs but their infection is abortive. Infection was associated with immunoregulatory cytokines secretion and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In vitro polarization did not account for permissivity to SARS-CoV-2, since M1- and M2-type MDMs were similarly infected. In Covid-19 patients, monocytes exhibited lower counts affecting all subsets, decreased expression of HLA-DR, and increased expression of CD163, irrespective of severity. Conclusion SARS-CoV-2 drives monocytes and macrophages to induce host immunoparalysis for the benefit of Covid-19 progression.
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