PMID- 18391002
OWN - NLM
STAT- MEDLINE
DCOM- 20080703
LR  - 20211020
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 76
IP  - 6
DP  - 2008 Jun
TI  - Inheritance of immune polarization patterns is linked to resistance versus 
      susceptibility to Cryptococcus neoformans in a mouse model.
PG  - 2379-91
LID - 10.1128/IAI.01143-07 [doi]
AB  - Genetic background variation between inbred strains accounts for different levels 
      of susceptibility to Cryptococcus neoformans in the mouse infection model. To 
      elucidate the inheritance of immunophenotypic traits and their associations with 
      clearance outcomes during cryptococcal infection, we compared C57BL/6, BALB/c, 
      and their first-generation hybrid, CB6F1 (F1), mice. Mice from each group were 
      infected with C. neoformans (10(4) CFU) and analyzed at weekly intervals over a 
      6-week period. BALB/c mice progressively cleared the cryptococcal infection in 
      the lungs and showed a Th1-skewed immune response: a Th1-shifted cytokine 
      profile, modest lung pathology, and no significant elevation in the systemic 
      immunoglobulin E (IgE) level. In contrast, C57BL/6 mice developed a chronic 
      infection with a Th2-skewed immune response: a Th2-shifted cytokine profile, 
      pulmonary eosinophilia, severe lung pathology, elevated serum IgE, fungemia, and 
      cryptococcal dissemination in the central nervous system. F1 mice demonstrated 
      intermediate resistance to C. neoformans, with a stronger resemblance to the 
      immunophenotype of the resistant (BALB/c) mice. F1 mice also demonstrated 
      enhanced pulmonary recruitment of lymphocytes, especially CD8(+) T cells, in 
      comparison to both parental strains, suggesting positive heterosis. We conclude 
      that the inheritance of traits responsible for early cytokine induction in the 
      infected lungs and dendritic-cell maturation/activation status in draining nodes 
      is responsible for the intermediate immune response polarization and clearance 
      outcome observed initially in the lungs of F1 mice. The enhanced pulmonary 
      lymphocyte recruitment could be responsible for a gradual shutdown of the 
      undesirable Th2 arm of the immune response and subsequently improved 
      anticryptococcal resistance in F1 mice.
FAU - Chen, Gwo-hsiao
AU  - Chen GH
AD  - VA Medical Center Ann Arbor, Ann Arbor, MI 48105, USA.
FAU - McNamara, David A
AU  - McNamara DA
FAU - Hernandez, Yadira
AU  - Hernandez Y
FAU - Huffnagle, Gary B
AU  - Huffnagle GB
FAU - Toews, Galen B
AU  - Toews GB
FAU - Olszewski, Michal A
AU  - Olszewski MA
LA  - eng
GR  - R01 HL064558/HL/NHLBI NIH HHS/United States
GR  - R01-HL64558/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080407
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
SB  - IM
MH  - Animals
MH  - Cryptococcosis/*genetics/*immunology
MH  - Cryptococcus neoformans/*immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Fungemia/genetics
MH  - Genetic Predisposition to Disease
MH  - Inflammation/genetics
MH  - Lung/cytology/metabolism/microbiology
MH  - Lung Diseases, Fungal/*genetics/*immunology/microbiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Pulmonary Eosinophilia/genetics
MH  - Time Factors
PMC - PMC2423067
EDAT- 2008/04/09 09:00
MHDA- 2008/07/04 09:00
PMCR- 2008/10/01
CRDT- 2008/04/09 09:00
PHST- 2008/04/09 09:00 [pubmed]
PHST- 2008/07/04 09:00 [medline]
PHST- 2008/04/09 09:00 [entrez]
PHST- 2008/10/01 00:00 [pmc-release]
AID - IAI.01143-07 [pii]
AID - 1143-07 [pii]
AID - 10.1128/IAI.01143-07 [doi]
PST - ppublish
SO  - Infect Immun. 2008 Jun;76(6):2379-91. doi: 10.1128/IAI.01143-07. Epub 2008 Apr 7.