Lung Mucosa Lining Fluid Modification of Mycobacterium tuberculosis to Reprogram Human Neutrophil Killing Mechanisms.
We have shown that human alveolar lining fluid (ALF) contains homeostatic hydrolases capable of altering the Mycobacterium tuberculosis cell wall and subsequently its interaction with human macrophages. Neutrophils are also an integral part of the host immune response to M. tuberculosis infection. Here we show that the human lung mucosa influences M. tuberculosis interaction with neutrophils, enhancing the intracellular killing of ALF-exposed M. tuberculosis and up-regulating the expression of tumor necrosis factor and interleukin 8. In contrast, ALF-exposed M. tuberculosis does not induce neutrophil apoptosis or necrosis, degranulation, or release of extracellular traps, and it decreases the oxidative response. These results suggest an important role for the human alveolar mucosa: increasing the innate capacity of the neutrophil to recognize and kill M. tuberculosis by favoring the use of intracellular mechanisms, while at the same time limiting neutrophil extracellular inflammatory responses to minimize their associated tissue damage.
Department of Microbial Infection and Immunity.
Jesús
J
Arcos
Department of Microbial Infection and Immunity.
Lauren E
LE
Diangelo
Department of Microbial Infection and Immunity.
Julia M
JM
Scordo
Department of Microbial Infection and Immunity.
Smitha J
SJ
Sasindran
Department of Microbial Infection and Immunity.
Juan I
JI
Moliva
Department of Microbial Infection and Immunity Center for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus.
Joanne
J
Turner
Department of Microbial Infection and Immunity Center for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus.
Jordi B
JB
Torrelles
D017209:Apoptosis; D001431:Bacteriological Techniques; D001826:Body Fluids / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha
alveolar lining fluid; innate immunity; lung surfactant; neutrophil; tuberculosis