Lung Mucosa Lining Fluid Modification of<i>Mycobacterium tuberculosis</i>to Reprogram Human Neutrophil Killing Mechanisms

Arcos, Jesus; Diangelo, Lauren; Scordo, Julia M.; Sasindran, Smitha J.; Moliva, Juan I.; Turner, Joanne; Torrelles, Jordi B.

doi:10.1093/infdis/jiv146

Cited by 38 publications

(101 citation statements)

References 49 publications

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“…Association was determined by counting the number of M.tb bacilli associated with ≥500 consecutive neutrophils per coverslip performed in replicate using phase-contrast and fluorescence microscopy, as previously described (3). …”

Section: Methodsmentioning

confidence: 99%

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

et al. 2017

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In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment that Mycobacterium tuberculosis (M.tb) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter the M.tb surface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on the M.tb cell wall surface and release of M.tb cell wall fragments into the environment. Typically, one of the first host immune cells at the site of M.tb infection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response to M.tb during infection. We hypothesized that exposure of neutrophils to ALF-induced M.tb released cell wall fragments would prime neutrophils to control M.tb infection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control of M.tb growth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-induced M.tb fragments could further contribute to the control of M.tb growth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site.

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Section: Methodsmentioning

confidence: 99%

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

et al. 2017

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“…Surface expression of activation and degranulation markers on human neutrophils was assessed by flow cytometry as we previously described 27 . Briefly, neutrophils were infected with healthy ALF-exposed P .…”

Section: Methodsmentioning

confidence: 99%

Modifications of Pseudomonas aeruginosa cell envelope in the cystic fibrosis airway alters interactions with immune cells

Hill

Scordo

Arcos

et al. 2017

Sci Rep

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Pseudomonas aeruginosa is a ubiquitous environmental organism and an opportunistic pathogen that causes chronic lung infections in the airways of cystic fibrosis (CF) patients as well as other immune-compromised individuals. During infection, P. aeruginosa enters the terminal bronchioles and alveoli and comes into contact with alveolar lining fluid (ALF), which contains homeostatic and antimicrobial hydrolytic activities, termed hydrolases. These hydrolases comprise an array of lipases, glycosidases, and proteases and thus, they have the potential to modify lipids, carbohydrates and proteins on the surface of invading microbes. Here we show that hydrolase levels between human ALF from healthy and CF patients differ. CF-ALF influences the P. aeruginosa cell wall by reducing the content of one of its major polysaccharides, Psl. This CF-ALF induced Psl reduction does not alter initial bacterial attachment to surfaces but reduces biofilm formation. Importantly, exposure of P. aeruginosa to CF-ALF drives the activation of neutrophils and triggers their oxidative response; thus, defining human CF-ALF as a new innate defense mechanism to control P. aeruginosa infection, but at the same time potentially adding to the chronic inflammatory state of the lung in CF patients.

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“…The best-characterized innate responses are those of phagocytic lineages: monocytes, macrophages/dendritic cells (DCs) and neutrophils, which each respond to prokaryotic and eukaryotic colonizers following the physical interaction of pattern recognition receptors (PRRs) with pathogen associated molecular patterns (PAMPs). Candida and Mycobacteria spp relationship to innate immune cells has been described as both “immune-evasive” and “immunostimulatory” 64, and the immunogenicity of Candida and Mycobacteria PAMPs varies depending on their environmental conditions 65–70 . C. albicans and most pathogenic Candida spp are pleomorphic fungi that grow as yeast, pseudohyphae or hyphae forms, and have an outer membrane comprising a lipid bilayer and polysaccharide-rich cell wall that promotes adherence to epithelial cells 71 .…”

Section: Innate Responses To Candida and Mycobacteria Speciesmentioning

confidence: 99%

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

Robinson

Huppler

2017

Cytokine

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Mycobacteria and Candida species include significant human pathogens that can cause localized or disseminated infections. Although these organisms may appear to have little in common, several shared pathways of immune recognition and response are important for both control and infection-related pathology. In this article, we compare and contrast the innate and adaptive components of the immune system that pertain to these infections in humans and animal models. We also explore a relatively new concept in the mycobacterial field: biological commensalism. Similar to the well-established model of Candida infection, Mycobacterial species colonize their human hosts in equilibrium with the immune response. Perturbations in the immune response permit the progression to pathologic disease at the expense of the host. Understanding the immune factors required to maintain commensalism may aid with the development of diagnostic and treatment strategies for both categories of pathogens.

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Lung Mucosa Lining Fluid Modification ofMycobacterium tuberculosisto Reprogram Human Neutrophil Killing Mechanisms

Cited by 38 publications

References 49 publications

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

Modifications of Pseudomonas aeruginosa cell envelope in the cystic fibrosis airway alters interactions with immune cells

The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

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