Contribution of IL-1 to resistance to Streptococcus pneumoniae infection.
The role of IL-1 in susceptibility to Streptococcus pneumoniae infection was studied in mice deficient in genes of the IL-1 family [i.e. IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/- and IL-1R antagonist (IL-1Ra)-/- mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1beta-/- and IL-1alpha/beta-/- mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1alpha-/- and IL-1Ra-/- mice. Treatment of IL-1beta-/- mice with rIL-1beta significantly improved their survival. A significant increase in blood neutrophils was found in control, IL-1alpha-/- and IL-1Ra-/- but not in IL-1beta-/- and IL-1alpha/beta-/- mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1alpha-/- and control mice. However, S. pneumoniae-infected IL-1beta-/-, IL-1alpha/beta-/- and IL-1Ra-/- mice demonstrated diffuse pneumonia and tissue damage. Altogether, all three isoforms contribute to protection against S. pneumoniae; our results point to differential role of IL-1alpha and IL-1beta in the pathogenesis and control of S. pneumoniae infection and suggest that IL-1beta has a major role in resistance to primary pneumococcal infection while the role of IL-1alpha is less important.
Kafka
Daniel
D
Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer Sheva 84101, Israel.
Ling
Eduard
E
Feldman
Galia
G
Benharroch
Daniel
D
Voronov
Elena
E
Givon-Lavi
Noga
N
Iwakura
Yoichiro
Y
Dagan
Ron
R
Apte
Ron N
RN
Mizrachi-Nebenzahl
Yaffa
Y
D000818:Animals; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D053582:Interleukin-1alpha / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009305:Nasopharynx / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000302:isolation & purification / Q000472:pathogenicity*
D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1