Toll-like receptor-4 agonist in post-haemorrhage pneumonia: role of dendritic and natural killer cells

Abstract

Haemorrhage-induced immunosuppression has been linked to nosocomial infections. We assessed the impact of monophosphoryl lipid A, a Toll/interleukin-1 receptor-domain-containing adaptor protein inducing interferon-biased Toll-like receptor-4 agonist currently used as a vaccine adjuvant in humans, on post-haemorrhage susceptibility to infection.We used a mouse model of post-haemorrhage pneumonia induced by methicillin-susceptible Staphylococcus aureus. Monophosphoryl lipid A was administered intravenously after haemorrhage and before pneumonia onset.Haemorrhage altered survival rate, increased lung damage (neutrophil accumulation, oedema and cytokine release) and altered the functions of dendritic and natural killer cells. Here, we show that monophosphoryl lipid A decreased systemic dissemination of S. aureus and dampened inflammatory lung lesions. Monophosphoryl lipid A partially restored the capacity for antigen presentation and the transcriptional activity in dendritic cells. Monophosphoryl lipid A did not restore the interferon-c mRNA but prevented interleukin-10 mRNA overexpression in natural killer cells compared with untreated mice. Ex vivo monophosphoryl lipid A-stimulated dendritic cells or natural killer cells harvested from haemorrhaged animals were adoptively transferred into mice undergoing post-haemorrhage pneumonia. Stimulated dendritic cells (but not stimulated natural killer cells) improved the survival rate compared with mice left untreated. In vivo depletion of natural killer cells decreased survival rate of monophosphoryl lipid A-treated mice.Dendritic and natural killer cells are critically involved in the beneficial effects of monophosphoryl lipid A within post-haemorrhage pneumonia. @ERSpublications Dendritic cells and NK cells are critically involved in the beneficial effects of MPLA within posthaemorrhage pneumonia

Assessment of the Partial Purified Lipid a Extracted from Proteus mirabiliscell Wall as Adjuvant Immunotherapy

“…The results showed the control group was infected with severe inflammation, abscess and subjected to death within five days, the death began at the second day after infection, while the immunized groups with prepared vaccine showed minor symptoms of inflammation and started to heal from the fifth day and the healing completed after a week from the booster dose. These results agreed with that reported by Roquillyet al, (45) …”

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

“…Intrapulmonary transfer of bone marrow-derived DCs restored DC function and prevented fatal Aspergillus fumigatus infection in mice that had recovered from primary peritonitis 66 . TLR agonists also improve survival from pneumonia occurring in mice after haemorrhagic shock 67,68 . A possible mechanism for the beneficial effect of TLR agonists includes increased MHC class II molecules, CD80 and CD86 expression on DCs 67,68 .…”

“…TLR agonists also improve survival from pneumonia occurring in mice after haemorrhagic shock 67,68 . A possible mechanism for the beneficial effect of TLR agonists includes increased MHC class II molecules, CD80 and CD86 expression on DCs 67,68 . Given these encouraging results, some authors have argued that preserving and/or restoring DC function should be a primary target of investigations in sepsis 63–69 .…”

Hydrocortisone Prevents Immunosuppression by Interleukin-10+ Natural Killer Cells After Trauma-Hemorrhage

“…1B). We then aimed to delineate the mechanisms explaining this IL-10 decrease, and we used a previously described mouse model of posthemorrhage pneumonia (19,20).…”

“…Twenty-four hours later, 7 × 10 5 colony-forming units of a methicillin-susceptible Staphylococcus aureus strain (ATCC 29213) were instilled in the trachea of anesthetized mice (for description of the study groups, see Fig. E1, Supplemental Digital Content 1, http://links.lww.com/CCM/B92) (19,20).…”