Streptococcus pyogenes CAMP factor attenuates phagocytic activity of RAW 264.7 cells.
Streptococcus pyogenes produces molecules that inhibit the function of human immune system, thus allowing the pathogen to grow and spread in tissues. It is known that S. pyogenes CAMP factor increases erythrocytosis induced by Staphylococcus aureus β-hemolysin. However, the effects of CAMP factor for immune cells are unclear. In this study, we investigated the effects of CAMP factor to macrophages. Western blotting analysis demonstrated that all examined strains expressed CAMP factor protein. In the presence of calcium or magnesium ion, CAMP factor was significantly released in the supernatant. In addition, both culture supernatant from S. pyogenes strain SSI-9 and recombinant CAMP factor dose-dependently induced vacuolation in RAW 264.7 cells, but the culture supernatant from Δcfa isogenic mutant strain did not. CAMP factor formed oligomers in RAW 264.7 cells in a time-dependent manner. CAMP factor suppressed cell proliferation via G2 phase cell cycle arrest without inducing cell death. Furthermore, CAMP factor reduced the uptake of S. pyogenes and phagocytic activity indicator by RAW 264.7 cells. These results suggest that CAMP factor works as a macrophage dysfunction factor. Therefore, we conclude that CAMP factor allows S. pyogenes to escape the host immune system, and contribute to the spread of streptococcal infection.
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan; Division of Pediatric Dentistry, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Mie
M
Kurosawa
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Masataka
M
Oda
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Hisanori
H
Domon
Division of Pediatric Dentistry, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Issei
I
Saitoh
Division of Pediatric Dentistry, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Haruaki
H
Hayasaki
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan. Electronic address: terao@dent.niigata-u.ac.jp.
Yutaka
Y
Terao
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D006460:Hemolysin Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects*; D000067996:RAW 264.7 Cells; D013297:Streptococcus pyogenes / Q000276:immunology*
D001426:Bacterial Proteins; C039092:CAMP protein, Streptococcus; D006460:Hemolysin Proteins
CAMP factor; Innate immunity; Phagocytosis; Streptococcus pyogenes; Virulence factor