RGD Reference Report - CD28 exerts protective and detrimental effects in a pulmonary model of paracoccidioidomycosis. - Rat Genome Database

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CD28 exerts protective and detrimental effects in a pulmonary model of paracoccidioidomycosis.

Authors: Felonato, M  Pina, A  Bernardino, S  Loures, FV  De Araujo, EF  Calich, VL 
Citation: Felonato M, etal., Infect Immun. 2010 Nov;78(11):4922-35. Epub 2010 Aug 16.
RGD ID: 5131616
Pubmed: PMID:20713624   (View Abstract at PubMed)
PMCID: PMC2976317   (View Article at PubMed Central)
DOI: DOI:10.1128/IAI.00297-10   (Journal Full-text)

T-cell immunity has been claimed as the main immunoprotective mechanism against Paracoccidioides brasiliensis infection, the most important fungal infection in Latin America. As the initial events that control T-cell activation in paracoccidioidomycosis (PCM) are not well established, we decided to investigate the role of CD28, an important costimulatory molecule for the activation of effector and regulatory T cells, in the immunity against this pulmonary pathogen. Using CD28-deficient (CD28(-/-)) and normal wild-type (WT) C57BL/6 mice, we were able to demonstrate that CD28 costimulation determines in pulmonary paracoccidioidomycosis an early immunoprotection but a late deleterious effect associated with impaired immunity and uncontrolled fungal growth. Up to week 10 postinfection, CD28(-/-) mice presented increased pulmonary and hepatic fungal loads allied with diminished production of antibodies and pro- and anti-inflammatory cytokines besides impaired activation and migration of effector and regulatory T (Treg) cells to the lungs. Unexpectedly, CD28-sufficient mice progressively lost the control of fungal growth, resulting in an increased mortality associated with persistent presence of Treg cells, deactivation of inflammatory macrophages and T cells, prevalent presence of anti-inflammatory cytokines, elevated fungal burdens, and extensive hepatic lesions. As a whole, our findings suggest that CD28 is required for the early protective T-cell responses to P. brasiliensis infection, but it also induces the expansion of regulatory circuits that lately impair adaptive immunity, allowing uncontrolled fungal growth and overwhelming infection, which leads to precocious mortality of mice.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CD28Humanparacoccidioidomycosis  ISOCd28 (Mus musculus) RGD 
Cd28Ratparacoccidioidomycosis  ISOCd28 (Mus musculus) RGD 
Cd28Mouseparacoccidioidomycosis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd28  (Cd28 molecule)

Genes (Mus musculus)
Cd28  (CD28 antigen)

Genes (Homo sapiens)
CD28  (CD28 molecule)


Additional Information