PMID- 21765962
OWN - NLM
STAT- MEDLINE
DCOM- 20111107
LR  - 20240324
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 5
IP  - 7
DP  - 2011 Jul
TI  - Structural and topographic dynamics of pulmonary histopathology and local 
      cytokine profiles in Paracoccidioides brasiliensis conidia-infected mice.
PG  - e1232
LID - 10.1371/journal.pntd.0001232 [doi]
LID - e1232
AB  - BACKGROUND: Paracoccidioidomycosis (PCM), an endemic systemic mycosis caused by 
      the fungus Paracoccidioides brasiliensis (Pb), usually results in severe lung 
      damage in patients. METHODS AND FINDINGS: Considering the difficulties to 
      sequentially study the infection in humans, this work was done in mice inoculated 
      intranasally with infective Pb-conidia. Lungs of control and Pb-infected mice 
      were studied after 2-hours, 4, 8, 12 and 16-weeks post-infection (p.i) in order 
      to define histopathologic patterns of pulmonary lesions, multiplex-cytokine 
      profiles and their dynamics during the course of this mycosis. Besides the 
      nodular/granulomatous lesions previously informed, results revealed additional 
      non-formerly described lung abnormalities, such as periarterial sheath 
      inflammation and pseudotumoral masses. The following chronologic stages occurring 
      during the course of the experimental infection were defined: Stage one (2-hours 
      p.i): mild septal infiltration composed by neutrophils and macrophages 
      accompanied by an intense "cytokine burst" represented by significant increases 
      in IL-1alpha, IL-1beta, IL-4, IL-5, IL-6, IL-10, IL12p70, IL-13, IL-17, Eotaxin, G-CSF, 
      MCP1, MIP1alpha, GM-CSF, IFN-gamma, MIP1beta and TNFalpha levels. Stage two (4-weeks p.i): 
      presence of nodules, evidence of incipient periarterial- and intense but disperse 
      parenchymal- inflammation, abnormalities that continued to be accompanied by 
      hyper-secretion of those cytokines and chemokines mentioned in the first stage of 
      infection. Stages three and four (8 and 12-weeks p.i.): fungal proliferation, 
      inflammation and collagenesis reached their highest intensity with particular 
      involvement of the periarterial space. Paradoxically, lung cytokines and 
      chemokines were down-regulated with significant decreases in 
      IL-2,IL-3,IL-5,IL-9,IL-13,IL-15,GM-CSF,IFN-gamma,MIP1beta and TNFalpha. Stage five (16-weeks 
      p.i.): inflammation decreased becoming limited to the pseudotumoral masses and 
      was accompanied by a "silent" cytokine response, except for PDGF, MIG, RANTES and 
      IL12p40 which remained up-regulated for the duration of the experiment. 
      CONCLUSIONS: Results of this study identified both classic and novel patterns 
      corresponding to histopathologic and immunologic responses occurring during the 
      course of experimental PCM.
FAU - Lopera, Damaris
AU  - Lopera D
AD  - Medical and Experimental Mycology Group, Corporacion para Investigaciones 
      Biologicas, Medellin, Colombia.
FAU - Naranjo, Tonny W
AU  - Naranjo TW
FAU - Cruz, Oswaldo G
AU  - Cruz OG
FAU - Restrepo, Angela
AU  - Restrepo A
FAU - Cano, Luz Elena
AU  - Cano LE
FAU - Lenzi, Henrique Leonel
AU  - Lenzi HL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110712
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - Histocytochemistry
MH  - Immunoassay
MH  - Immunohistochemistry
MH  - Lung/microbiology/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microscopy
MH  - Paracoccidioides/*immunology/*pathogenicity
MH  - Paracoccidioidomycosis/*immunology/*pathology
MH  - Rodent Diseases/immunology/pathology
MH  - Spores, Fungal/immunology/pathogenicity
MH  - Time Factors
PMC - PMC3134433
COIS- The authors have declared that no competing interests exist.
EDAT- 2011/07/19 06:00
MHDA- 2011/11/08 06:00
PMCR- 2011/07/12
CRDT- 2011/07/19 06:00
PHST- 2010/09/29 00:00 [received]
PHST- 2011/05/25 00:00 [accepted]
PHST- 2011/07/19 06:00 [entrez]
PHST- 2011/07/19 06:00 [pubmed]
PHST- 2011/11/08 06:00 [medline]
PHST- 2011/07/12 00:00 [pmc-release]
AID - PNTD-D-10-00033 [pii]
AID - 10.1371/journal.pntd.0001232 [doi]
PST - ppublish
SO  - PLoS Negl Trop Dis. 2011 Jul;5(7):e1232. doi: 10.1371/journal.pntd.0001232. Epub 
      2011 Jul 12.