Mycobacterium avium infection of epithelial cells results in inhibition or delay in the release of interleukin-8 and RANTES.
Mycobacterium avium is an opportunistic pathogen in AIDS patients, who acquire the infection mainly through the gastrointestinal tract. Previous studies in vitro have shown that M. avium invades epithelial cells of both intestinal and laryngeal origin. In addition, M. avium enters the intestinal mucosa of healthy mice. Because M. avium invasion of the intestinal mucosa in vivo initially is not accompanied by significant influx of inflammatory cells, we sought to determine whether M. avium would trigger chemokine release upon entry into epithelial cells by using HT-29 intestinal and HEp-2 laryngeal epithelial cell lines. Chemokine synthesis was measured both by the presence of specific mRNA and protein secretion in the cell culture supernatant as determined by enzyme-linked immunosorbent assay. Infection of HT-29 intestinal cells with M. avium did not induce the release of interleukin-8 (IL-8) or RANTES for up to 7 days postinfection. However, infection of HEp-2 cells resulted in the release of IL-8 and RANTES at 72 h. Similar findings were observed with other AIDS M. avium isolates belonging to different serovars. Secretion of IL-8 by HEp-2 cells was dependent upon bacterial uptake. In addition, prior infection with M. avium suppressed IL-8 production by HT-29 cells infected with Salmonella typhimurium. Our results suggest that M. avium infection of epithelial cells is associated with a delay in IL-8 and RANTES production which, in the case of HT-29, is prolonged up to 1 week. These findings may explain the weak inflammatory response after intestinal mucosa invasion in mice and are probably related with the ability of the bacterium to evade the host's immune response.
Sangari
F J
FJ
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, California 94115, USA.
Petrofsky
M
M
Bermudez
L E
LE
D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology; D019073:HT29 Cells; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D009162:Mycobacterium avium / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012475:Salmonella / Q000502:physiology
D018946:Chemokine CCL5; D016209:Interleukin-8; D012333:RNA, Messenger