The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

Abstract

Previously, we demonstrated that the nasal administration of Dolosigranulum pigrum 040417 differentially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 2 in infant mice. In this work, we aimed to evaluate the beneficial effects of D. pigrum 040417 in the context of Streptococcus pneumoniae infection and characterize the role of alveolar macrophages (AMs) in the immunomodulatory properties of this respiratory commensal bacterium. The nasal administration of D. pigrum 040417 to infant mice significantly increased their resistance to pneumococcal infection, differentially modulated respiratory cytokines production, and reduced lung injuries. These effects were associated to the ability of the 040417 strain to modulate AMs function. Depletion of AMs significantly reduced the capacity of the 040417 strain to improve both the reduction of pathogen loads and the protection against lung tissue damage. We also demonstrated that the immunomodulatory properties of D. pigrum are strain-specific, as D. pigrum 030918 was not able to modulate respiratory immunity or to increase the resistance of mice to an S. pneumoniae infection. These findings enhanced our knowledge regarding the immunological mechanisms involved in modulation of respiratory immunity induced by beneficial respiratory commensal bacteria and suggested that particular strains could be used as next-generation probiotics.

Analysis of 16S rRNA Gene Sequence of Nasopharyngeal Exudate Reveals Changes in Key Microbial Communities Associated with Aging

“…This suggests that the relative abundance of Dolosigranulum may be higher in elderly people due to the process of immunosenescence that occurs in them [ 41 , 42 ], or that its higher abundance may be due to other unidentified age-related factors. Nevertheless, the relevance of Dolosigranulum in the nasopharynx deserved further investigation, since nasal administration Dolosigranulum pigrum 040417 to mice increased the resistance against respiratory syncytial virus (RSV) and Streptococcus pneumoniae [ 43 , 44 ]. However, other strains of the same species failed to protect mice against these pathogens [ 43 , 44 ].…”

“…Nevertheless, the relevance of Dolosigranulum in the nasopharynx deserved further investigation, since nasal administration Dolosigranulum pigrum 040417 to mice increased the resistance against respiratory syncytial virus (RSV) and Streptococcus pneumoniae [ 43 , 44 ]. However, other strains of the same species failed to protect mice against these pathogens [ 43 , 44 ]. Another interesting observation of our study is that Haemophilus that causes pneumonia mainly in elderly people [ 45 ] is underrepresented precisely in individuals over 70 years of age.…”

Genomic and Immunological Characterization of Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Isolates from Northwest Argentina

“…Antibiotic treatment decreased NF-κB and caspase-1/NLRP3 inflammasome signaling pathways, attenuating abnormally elevated levels of TNF-α, IL-1β, IL-6, and IL-17, thereby increasing the survival of infected mice. Together, these findings indicate that protection against respiratory infection caused by K. pneumoniae is achieved by inducing an inflammatory response capable of eliminating the pathogen, which must be efficiently regulated to prevent inflammatory damage and preserve lung function, as has been described for other bacterial [35,36] and viral [37,38] respiratory pathogens. Kinetics studies of inflammatory cells and factors both in the respiratory tract and blood would be of value to understand why, even though LABACER01 induced a more notorious inflammatory response than LABACER27, it was the strain with the greatest capacity to colonize the lung and spread into the blood.…”

Design and validation of Dolosigranulum pigrum specific PCR primers using the bacterial core genome

“…Dolosigranulum pigrum is gaining interest as a member of the upper respiratory tract microbial community that is potentially beneficial for the host 5 , 6 , 8 , 13 – 19 . Efforts are being made to better understand its metabolic models and defense mechanisms 20 .…”

“…Our assay was also highly sensitive and specific for detecting D. pigrum in clinical samples. Dolosigranulum pigrum is gaining interest as a member of the upper respiratory tract microbial community that is potentially beneficial for the host 5,6,8,[13][14][15][16][17][18][19] . Efforts are being made to better understand its metabolic models and defense mechanisms 20 .…”