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.
Highlights
The outcome of infections with a given microbial pathogen can vary considerably in different individuals, with some experiencing minimal clinical symptoms and others suffering severe disease or death
The factors that predispose individuals to develop severe Listeria monocytogenes (Lm) infection are not well understood, systemic infections require bacteria to disseminate from the intestines to the bloodstream and peripheral tissues
These lung exposures increase the survival and expansion of Lm that disseminate from the intestines to peripheral tissues by stimulating release of regulatory proteins that dampen the ability of myeloid cells to kill Lm
Summary
The outcome of infections with a given microbial pathogen can vary considerably in different individuals, with some experiencing minimal clinical symptoms and others suffering severe disease or death. This variability in disease phenotype is evident in the ongoing COVID-19 pandemic [1,2]. It has been estimated that concomitant infections are present in over one sixth of the world’s population [4] Many such coinfections are associated with more severe disease pathology [4], and some–including HIV and Mycobacterium tuberculosis (Mtb) or influenza virus and Streptococcus pneumoniae (Spn)–are frequently associated with mortality [5,6]. Skewing of cytokine profiles and myeloid cell responses correlates with increased disease severity and systemic bacterial dissemination during influenza:Spn coinfection [8,9]
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