A regulatory role for interleukin 4 in differential inflammatory responsesin the lung following infection of mice primed with Th1-or Th2-inducing pertussis vaccines
P. Mcguirk et Khg. Mills, A regulatory role for interleukin 4 in differential inflammatory responsesin the lung following infection of mice primed with Th1-or Th2-inducing pertussis vaccines, INFEC IMMUN, 68(3), 2000, pp. 1383-1390
Protection against infectious pathogens at mucosal surfaces is dependent on
local antibody responses, production of inflammatory mediators, and recrui
tment of immune effector cells to the site of infection. Since Th1 and Th2
cells produce cytokines with pro- and anti-inflammatory activities, immuniz
ation with vaccines that induce these T-cell subtypes may regulate the subs
equent inflammatory response to infection. We have demonstrated that immuni
zation of mice with pertussis whole-cell or acellular vaccines (Pw or Pa) s
electively induces Th1 and Th2 cells, respectively. In this study we have u
sed a murine respiratory-infection model to demonstrate that priming with a
Th1- or Th2-inducing pertussis vaccine can influence the local inflammator
y response and immune effector cells in the lung following aerosol challeng
e with Bordetella pertussis. Analysis of bronchoalveolar lavage (BAL) fluid
taken during the course of B. pertussis infection of naive mice or mice im
munized with Pw revealed an early influx of neutrophils and local productio
n of interleukin 1 beta (IL-1 beta) in the lungs. In contrast, neutrophil i
nfiltration and IL-1 beta production were not observed following challenge
of mice immunized with the Th2-inducing Pa. Conversely, during infection lo
cal production of IL-6 and IL-1ra was significantly greater in mice immuniz
ed with Pa than in those immunized with Pw. Studies of knockout mice reveal
ed neutrophil and lymphocyte infiltration in the lungs following B. pertuss
is infection of IL-4-defective (IL-4(-/-)) mice but not in wild-type mice i
mmunized with Pa. Furthermore, the levels of IL-1 beta, IL-6, and IL-1ra in
Pa-immunized IL-4(-/-) mice were comparable to those in mice immunized wit
h Pw. These results demonstrate distinct influences of Th1- and Th2-inducin
g vaccines on the protective inflammatory responses in the lungs following
challenge with B. pertussis and implicate IL-4 as an important regulator of
inflammatory-cell recruitment.