Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0022568 (
keratitis
)
5,133
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Why ocular mucosa is paucibacterial is unknown. Many different mechanisms have been suggested but the comprehensive experimental studies are sparse. We found that a deficiency in
L-plastin
(LCP1), an actin bundling protein, resulted in an ocular commensal overgrowth, characterized with increased presence of conjunctival
Streptococcal
spp. The commensal overgrowth correlated with susceptibility to
P. aeruginosa
-induced
keratitis
.
L-plastin
knock-out (KO) mice displayed elevated bacterial burden in the
P. aeruginosa
-infected corneas, altered inflammatory responses, and compromised bactericidal activity. Mice with ablation of LPL under the LysM Cre (
LysM. Cre
pos
LPL
fl
/
fl
) and S100A8 Cre (
S100A8.Cre
pos
LPL
fl
/
fl
) promoters had a similar phenotype to the LPL KOs mice. In contrast, infected
CD11c.Cre
pos
LPL
fl
/
fl
mice did not display elevated susceptibility to infection, implicating the myeloid
L-plastin
-sufficient cells (e.g., macrophages and neutrophils) in maintaining ocular homeostasis. Mechanistically, the elevated commensal burden and the susceptibility to infection were linked to defects in neutrophil frequencies at steady state and during infection and compromised bactericidal activities upon priming. Macrophage exposure to commensal organisms primed neutrophil responses to
P. aeruginosa
, augmenting PMN bactericidal capacity in an
L-plastin
dependent manner. Cumulatively, our data highlight the importance of neutrophils in controlling ocular paucibacteriality, reveal molecular and cellular events involved in the process, and suggest a link between commensal exposure and resistance to infection.
...
PMID:Neutrophil L-Plastin Controls Ocular Paucibacteriality and Susceptibility to Keratitis. 3231 63
