Enhanced Mucosal Antibody Production and Protection against Respiratory Infections Following an Orally Administered Bacterial Extract.

Christian Pasquali,Manisha Taneja,Aurelien Trompette,Cã©Line Pattaroni,Koshika Yadava,Olawale Salami,Jacques Bauer,Benjamin J Marsland,Eva S Gollwitzer

doi:10.3389/fmed.2014.00041

Christian Pasquali, Manisha Taneja + Show 7 more

Open Access

https://doi.org/10.3389/fmed.2014.00041

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Abstract

Secondary bacterial infections following influenza infection are a pressing problem facing respiratory medicine. Although antibiotic treatment has been highly successful over recent decades, fatalities due to secondary bacterial infections remain one of the leading causes of death associated with influenza. We have assessed whether administration of a bacterial extract alone is sufficient to potentiate immune responses and protect against primary infection with influenza, and secondary infections with either Streptococcus pneumoniae or Klebsiella pneumoniae in mice. We show that oral administration with the bacterial extract, OM-85, leads to a maturation of dendritic cells and B-cells characterized by increases in MHC II, CD86, and CD40, and a reduction in ICOSL. Improved immune responsiveness against influenza virus reduced the threshold of susceptibility to secondary bacterial infections, and thus protected the mice. The protection was associated with enhanced polyclonal B-cell activation and release of antibodies that were effective at neutralizing the virus. Taken together, these data show that oral administration of bacterial extracts provides sufficient mucosal immune stimulation to protect mice against a respiratory tract viral infection and associated sequelae.

Highlights

Recurrent respiratory tract infections (RTIs) are a leading cause of morbidity and mortality, with therapeutic options largely limited to traditional antibiotic treatments [1]
Mice treated with OM-85 had a lower viral load in the lung tissue on day 5 post-infection as compared to mice treated with the control solution, which had undergone the same manufacturing process as OM-85, but without the bacterial extracts (Figure 1B)
OM-85 ENHANCES DENDRITIC CELL MATURATION Given the protective effect of OM-85 against viral infections and secondary bacterial infections, we investigated how OM-85 shaped dendritic cell (DC) activation states, considering that DCs are one of the most potent cell types that influence immunity and have recently been shown to be activated by OM-85 [26]

Summary

Introduction

Recurrent respiratory tract infections (RTIs) are a leading cause of morbidity and mortality, with therapeutic options largely limited to traditional antibiotic treatments [1]. An alternative approach is the direct administration of purified microbial components or bacterial extracts that provide maturation signals to the immune system [6,7,8,9]. Both clinical and experimental studies have shown that administration of bacterial extracts can be efficacious in numerous disease settings such as chronic obstructive pulmonary disease, recurrent respiratory and urinary tract infections of bacterial or viral origins, wheezing lower respiratory illness (WLRI), and subsequent asthma [10, 11]

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