Efficient resolution of Pneumocystis murina infection in surfactant protein A-deficient mice following withdrawal of corticosteroid-induced immunosuppression
Following withdrawal of immunosuppression, surfactant protein A (SP-A)-deficient and wild-type mice cleared Pneumocystis murina infection in a similar manner, but exhibited significant differences in lymphocyte populations, interleukin (IL)-6 levels and chemokine expression levels. A higher percentage of lymphocytes were detected in lung lavage fluid from SP-A-deficient mice, but more CD4+ T cells were isolated from lung tissue of wild-type mice. Higher concentrations of IL-6 were detected in lavage fluid and enhanced expression of lymphotactin and RANTES were detected in the lungs of wild-type mice. Equal levels of surfactant protein D were detected in SP-A-deficient and wild-type mice and no differences were detected in markers of lung injury between the two strains of mice. Thus, SP-A does not enhance organism clearance, but does modulate the host immune response during resolution of P. murina infection.
AtochinaE. N.,
BeckJ. M.,
PrestonA. M. & 8 other authors; 2004; Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice: attenuation of cytokine responses and reactive oxygen-nitrogen species. Infect Immun 72:6002–6011[CrossRef]
BarryS. M.,
LipmanM. C.,
DeeryA. R.,
JohnsonM. A.,
JanossyG.2002; Immune reconstitution pneumonitis following Pneumocystis carinii pneumonia in HIV-infected subjects. HIV Med 3:207–211[CrossRef]
ChenW.,
HavellE. A.,
GigliottiF.,
HarmsenA. G.1993; Interleukin-6 production in a murine model of Pneumocystis carinii pneumonia: relation to resistance and inflammatory response. Infect Immun 61:97–102
ElhalwagiB. M.,
ZhangM.,
IkegamiM.,
IwamotoH. S.,
MorrisR. E.,
MillerM. L.,
DiengerK.,
McCormackF. X.1999; Normal surfactant pool sizes and inhibition-resistant surfactant from mice that overexpress surfactant protein A. Am J Respir Cell Mol Biol 21:380–387[CrossRef]
GoldJ. A.,
HoshinoY.,
TanakaN.,
RomW. N.,
RajuB.,
CondosR.,
WeidenM. D.2004; Surfactant protein A modulates the inflammatory response in macrophages during tuberculosis. Infect Immun 72:645–650[CrossRef]
KovalC. E.,
GigliottiF.,
NevinsD.,
DemeterL. M.2002; Immune reconstitution syndrome after successful treatment of Pneumocystis carinii pneumonia in a man with human immunodeficiency virus type 1 infection. Clin Infect Dis 35:491–493[CrossRef]
LeVineA. M.,
BrunoM. D.,
HuelsmanK. M.,
RossG. F.,
WhitsettJ. A.,
KorfhagenT. R.1997; Surfactant protein A-deficient mice are susceptible to group B streptococcal infection. J Immunol 158:4336–4340
LeVineA. M.,
KurakK. E.,
BrunoM. D.,
StarkJ. M.,
WhitsettJ. A.,
KorfhagenT. R.1998; Surfactant protein-A-deficient mice are susceptible to Pseudomonas aeruginosa infection. Am J Respir Cell Mol Biol 19:700–708[CrossRef]
LimperA. H.,
OffordK. P.,
SmithT. F.,
MartinW. J.1989; Pneumocystis carinii pneumonia. Differences in lung parasite number and inflammation in patients with and without AIDS. Am Rev Respir Dis 140:1204–1209[CrossRef]
LinkeM. J.,
HarrisC. E.,
KorfhagenT. R.,
McCormackF. X.,
AshbaughA. D.,
SteeleP.,
WhitsettJ. A.,
WalzerP. D.2001; Immunosuppressed surfactant protein A-deficient mice have increased susceptibility to Pneumocystis carinii infection. J Infect Dis 183:943–952[CrossRef]
LinkeM.,
AshbaughA.,
KochJ.,
TanakaR.,
WalzerP.2005; Surfactant protein A limits Pneumocystis murina infection in immunosuppressed C3H/HeN mice and modulates host response during infection. Microbes Infect 7:748–759[CrossRef]
McCormackF. X.,
WhitsettJ. A.2002; The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest 109:707–712[CrossRef]
McNeelyT. B.,
CoonrodJ. D.1993; Comparison of the opsonic activity of human surfactant protein A for Staphylococcus aureus and Streptococcus pneumoniae with rabbit and human macrophages. J Infect Dis 167:91–97[CrossRef]
SepkowitzK. A.2002; Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. Clin Infect Dis 34:1098–1107[CrossRef]
ThullenT. D.,
AshbaughA. D.,
DalyK. R.,
LinkeM. J.,
SteeleP. E.,
WalzerP. D.2004; Sensitized splenocytes result in deleterious cytokine cascade and hyperinflammatory response in rats with Pneumocystis pneumonia despite the presence of corticosteroids. Infect Immun 72:757–765[CrossRef]
Van IwaardenJ. F.,
PikaarJ. C.,
StormJ.,
BrouwerE.,
VerhoefJ.,
OostingR. S.,
van GoldeL. M.,
van StrijpJ. A.1994; Binding of surfactant protein A to the lipid A moiety of bacterial lipopolysaccharides. Biochem J 303:407–411
WalzerP. D.,
LaBineM.,
RedingtonT. J.,
CushionM. T.1984; Lymphocyte changes during chronic administration of and withdrawal from corticosteroids: relation to Pneumocystis carinii pneumonia. J Immunol 133:2502–2508
WalzerP. D.,
StanforthD.,
LinkeM. J.,
CushionM. T.1987; Pneumocystis carinii : immunoblotting and immunofluorescent analyses of serum antibodies during experimental rat infection and recovery. Exp Parasitol 63:319–328[CrossRef]
WuH.,
KuzmenkoA.,
WanS.,
SchafferL.,
WeissA.,
FisherJ. H.,
KimK. S.,
McCormackF. X.2003; Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. J Clin Invest 111:1589–1602[CrossRef]
ZimmermanP. E.,
VoelkerD. R.,
McCormackF. X.,
PaulsrudJ. R.,
MartinW. J.1992; 120-kD surface glycoprotein of Pneumocystis carinii is a ligand for surfactant protein A. J Clin Invest 89:143–149[CrossRef]
Efficient resolution of Pneumocystis murina infection in surfactant protein A-deficient mice following withdrawal of corticosteroid-induced immunosuppression