PMID- 15618139
OWN - NLM
STAT- MEDLINE
DCOM- 20050112
LR  - 20230427
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 73
IP  - 1
DP  - 2005 Jan
TI  - Transient neutralization of tumor necrosis factor alpha can produce a chronic 
      fungal infection in an immunocompetent host: potential role of immature dendritic 
      cells.
PG  - 39-49
AB  - The mechanisms underlying induction of immune dysregulation and chronic fungal 
      infection by a transient tumor necrosis factor alpha (TNF-alpha) deficiency 
      remain to be defined. The objective of our studies was to determine the potential 
      contribution of neutropenia and immature dendritic cells to the immune deviation. 
      Administration of an anti-TNF-alpha monoclonal antibody at day 0 neutralized 
      TNF-alpha only during the first week of a pulmonary Cryptococcus neoformans 
      infection. Transient neutralization of TNF-alpha resulted in transient depression 
      of interleukin-12 (IL-12), monocyte chemotactic protein 1 (MCP-1), and gamma 
      interferon (IFN-gamma) production but permanently impaired long-term clearance of 
      the infection from the lungs even after the levels of these cytokines increased 
      and a vigorous inflammatory response developed. Early neutrophil recruitment was 
      defective in the absence of TNF-alpha. However, as demonstrated by neutrophil 
      depletion studies, this did not account for the decrease in IL-12 and IFN-gamma 
      levels and did not play a role in establishing chronic pulmonary cryptococcal 
      infection. Transient TNF-alpha neutralization also produced a deficiency in 
      CD11c(+) MHC II(+) cells and IL-12 in the lymph nodes, potentially implicating a 
      defect in mature dendritic cell trafficking. Transfer of cryptococcal 
      antigen-pulsed immature dendritic cells into naive mice prior to intratracheal 
      challenge resulted in the development of a nonprotective immune response to C. 
      neoformans that was similar to that observed in anti-TNF-alpha-treated mice 
      (increased IL-4, IL-5, and IL-10 levels, pulmonary eosinophilia, and decreased 
      clearance). Thus, stimulation of an antifungal response by immature dendritic 
      cells can result in an immune deviation similar to that produced by transient 
      TNF-alpha deficiency, identifying a new mechanism by which a chronic fungal 
      infection can occur in an immunocompetent host.
FAU - Herring, Amy C
AU  - Herring AC
AD  - Pulmonary and Critical Care Medicine, 6301 MSRB III, The University of Michigan, 
      Ann Arbor, MI 48109-0642, USA.
FAU - Falkowski, Nicole R
AU  - Falkowski NR
FAU - Chen, Gwo-Hsiao
AU  - Chen GH
FAU - McDonald, Rod A
AU  - McDonald RA
FAU - Toews, Galen B
AU  - Toews GB
FAU - Huffnagle, Gary B
AU  - Huffnagle GB
LA  - eng
GR  - T32 HL007749/HL/NHLBI NIH HHS/United States
GR  - T32-HL07749/HL/NHLBI NIH HHS/United States
GR  - R01-HL51082/HL/NHLBI NIH HHS/United States
GR  - R01-HL65912/HL/NHLBI NIH HHS/United States
GR  - R01 HL051082/HL/NHLBI NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01 HL065912/HL/NHLBI NIH HHS/United States
GR  - R01-HL63670/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/biosynthesis
MH  - Chronic Disease
MH  - Cryptococcosis/*immunology
MH  - Dendritic Cells/*physiology
MH  - Immunocompetence
MH  - Interleukin-12/biosynthesis
MH  - Leukocytes/physiology
MH  - Lung Diseases, Fungal/*immunology
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Mycoses/*immunology
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/deficiency/*physiology
PMC - PMC538928
EDAT- 2004/12/25 09:00
MHDA- 2005/01/13 09:00
PMCR- 2005/01/01
CRDT- 2004/12/25 09:00
PHST- 2004/12/25 09:00 [pubmed]
PHST- 2005/01/13 09:00 [medline]
PHST- 2004/12/25 09:00 [entrez]
PHST- 2005/01/01 00:00 [pmc-release]
AID - 73/1/39 [pii]
AID - 0530-04 [pii]
AID - 10.1128/IAI.73.1.39-49.2005 [doi]
PST - ppublish
SO  - Infect Immun. 2005 Jan;73(1):39-49. doi: 10.1128/IAI.73.1.39-49.2005.