DNAX-activating protein of 12 kDa impairs host defense in pneumococcal pneumonia.

Abstract

OBJECTIVES:

Streptococcus pneumoniae is the most common causative organism in community-acquired pneumonia responsible for millions of deaths every year. DNAX-activating protein of 12 kDa is an adaptor molecule for different myeloid expressed receptors involved in innate immunity.

DESIGN:

Animal study.

SETTING:

University research laboratory.

SUBJECTS:

DNAX-activating protein of 12 kDa-deficient (dap12) and wild-type mice.

INTERVENTIONS:

Mice were intranasally infected with S. pneumoniae. In addition, ex vivo responsiveness of alveolar macrophages was examined.

MEASUREMENTS AND MAIN RESULTS:

dap12 alveolar macrophages released more tumor necrosis factor-α upon stimulation with S. pneumoniae and displayed increased phagocytosis of this pathogen compared with wild-type cells. After infection with S. pneumoniae via the airways, dap12 mice demonstrated reduced bacterial outgrowth in the lungs together with delayed dissemination to distant body sites relative to wild-type mice. This favorable response in dap12 mice was accompanied by reduced lung inflammation and an improved survival.

CONCLUSIONS:

These data suggest that DNAX-activating protein of 12 kDa impairs host defense during pneumococcal pneumonia at the primary site of infection at least in part by inhibiting phagocytosis by alveolar macrophages.

• Authors: Tijmen J Hommes, Arie J Hoogendijk, Mark C Dessing, Cornelis Van't Veer, Sandrine Florquin, Alex F de Vos, Tom van der Poll
• Journal: Critical care medicine (Crit Care Med) Vol. 42 Issue 12 Pg. e783-90 (Dec 2014) ISSN: 1530-0293 [Electronic] United States
• PMID: 25402298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Membrane Glycoproteins
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Tyrobp protein, mouse

Topics

• Adaptor Proteins, Signal Transducing (immunology)
• Animals
• Inflammation (immunology)
• Macrophages, Alveolar (immunology)
• Membrane Glycoproteins
• Mice
• Mice, Inbred C57BL
• Phagocytosis (immunology)
• RNA, Messenger (biosynthesis)
• Streptococcus pneumoniae (immunology)
• Tumor Necrosis Factor-alpha (biosynthesis)