1. Pulmonary insults exacerbate susceptibility to oral Listeria monocytogenes infection through the production of IL-10 by NK cells.
- Author
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Bortell N, Aguilera ER, and Lenz LL
- Subjects
- Animals, Disease Progression, Disease Susceptibility, Female, Interleukin-10 metabolism, Killer Cells, Natural metabolism, Killer Cells, Natural physiology, Lipopolysaccharides, Listeria monocytogenes pathogenicity, Listeriosis complications, Listeriosis pathology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mouth Diseases complications, Mouth Diseases immunology, Mouth Diseases microbiology, Mouth Diseases pathology, Pneumonia complications, Pneumonia etiology, Pneumonia pathology, Listeria monocytogenes immunology, Listeriosis immunology, Pneumonia immunology
- Abstract
Most individuals who consume foods contaminated with the bacterial pathogen Listeria monocytogenes (Lm) develop mild symptoms, while others are susceptible to life-threatening systemic infections (listeriosis). Although it is known that the risk of severe disease is increased in certain human populations, including the elderly, it remains unclear why others who consume contaminated food develop listeriosis. Here, we used a murine model to discover that pulmonary coinfections can impair the host's ability to adequately control and eradicate systemic Lm that cross from the intestines to the bloodstream. We found that the resistance of mice to oral Lm infection was dramatically reduced by coinfection with Streptococcus pneumoniae (Spn), a bacterium that colonizes the respiratory tract and can also cause severe infections in the elderly. Exposure to Spn or microbial products, including a recombinant Lm protein (L1S) and lipopolysaccharide (LPS), rendered otherwise resistant hosts susceptible to severe systemic Lm infection. In addition, we show that this increase in susceptibility was dependent on an increase in the production of interleukin-10 (IL-10) from Ncr1+ cells, including natural killer (NK) cells. Lastly, the ability of Ncr1+ cell derived IL-10 to increase disease susceptibility correlated with a dampening of both myeloid cell accumulation and myeloid cell phagocytic capacity in infected tissues. These data suggest that efforts to minimize inflammation in response to an insult at the respiratory mucosa render the host more susceptible to infections by Lm and possibly other pathogens that access the oral mucosa., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LLL is inventor on a patent describing use of the L1S protein for stimulation of immune responses.
- Published
- 2021
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