TY - JOUR
T1 - Impact of bacterial toxins in the lungs
AU - Lucas, Rudolf
AU - Hadizamani, Yalda
AU - Gonzales, Joyce
AU - Gorshkov, Boris A
AU - Bodmer, Thomas
AU - Berthiaume, Yves
AU - Moehrlen, Ueli
AU - Lode, Hartmut
AU - Huwer, Hanno
AU - Hudel, Martina
AU - Mraheil, Mobarak Abu
AU - Flores Toque, Haroldo Alfredo
AU - Chakraborty, Trinad
AU - Hamacher, Jürg
N1 - Funding Information:
Funding: The work of Juerg Hamacher, Yalda Hadizamani, Boris Gorshkov and Rudolf Lucas was supported by the Lungen-und Atmungsstiftung, Bern, 3012 Bern, Switzerland. Trinad Chakraborty and Mobarak A Mraheil report support from the DFG through TR84 “Innate Immunity of the lung” for data discussed in this manuscript. Rudolf Lucas was supported by NIH/NHLBI R01 grant HL138410.
Funding Information:
The work of Juerg Hamacher, Yalda Hadizamani, Boris Gorshkov and Rudolf Lucas was supported by the Lungen-und Atmungsstiftung, Bern, 3012 Bern, Switzerland. Trinad Chakraborty and Mobarak A Mraheil report support from the DFG through TR84 "Innate Immunity of the lung" for data discussed in this manuscript. Rudolf Lucas was supported by NIH/NHLBI R01 grant HL138410.
Publisher Copyright:
© 2020 by the authors.
PY - 2020/4
Y1 - 2020/4
N2 - Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na+ transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung's innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression.
AB - Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na+ transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung's innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression.
KW - Alveolar liquid clearance
KW - Alveolar-capillary barrier
KW - Bacterial toxins
KW - Host defense
KW - Inflammation
KW - Pulmonary edema
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U2 - 10.3390/toxins12040223
DO - 10.3390/toxins12040223
M3 - Article
C2 - 32252376
AN - SCOPUS:85083072099
SN - 2072-6651
VL - 12
JO - Toxins
JF - Toxins
IS - 4
M1 - 223
ER -