CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Mouse â defensins regulation during Vulvovaginal Candidiasis (VVC)
Autor/es:
MIRó MS; ICELY PA; SOTOMAYOR CE
Lugar:
Los Cocos. Cordoba
Reunión:
Congreso; LXI reunión científica anual de la Sociedad Argentina de Inmunología,; 2013
Institución organizadora:
Socieda Argentina de Inmunologia
Resumen:
Candida albicans (Ca) is a common commensal of mucosal surfaces and the most frequent
cause of VVC. Antimicrobial peptides like â-defensins (BDs) are a crucial component of the host
defence at mucosal epithelia. BDs exert antimicrobial and chemoattractant activities. Human
BD1 (mouse BD1 orthologous) is constitutively expressed in normal tissue, while BD3 (mouse
BD14 orthologous) can be induced by inflammation and microorganisms. Herein, we aimed to
study Ca ability to modulate local expression of BDs in mouse models of VVC. Female TLR2-
KO and C57BL/6 wt mice were used. Estrus phase was induced by estradiol injections. Infected
animals (Inf) were intravaginally inoculated with 5.106 Ca ATCC 36801 at day (D) 0. Untreated
uninfected mice were included as controls. At different D of infection, vaginal lavage was
obtained to evaluate fungal burden (CFU) and cytokine levels (ELISA); vaginas were removed
for histological studies (PAS) and RNA analisys. At D2 fungal burden in WT was lower than KO
(p<0,05). IL-1â and IL-6 did not exhibit changes in wt-Inf but an increase of both cytokines was
observed in KO mice (p<0,05). Histological studies showed a major presence of invasive
morphotype in the stratum corneum of KO mice; inflammation was characterized by mild PMNC
infiltration in wt mice and intraepithelial abscesses in KO mice. Expression of mBD1 and mBD14
mRNA transcripts showed disminished levels in wt-Inf animals while KO mice exhibited
increased levels of both BDs (p<0,05). Progression of the infection (D4) revealed major fungal
burden in wt than KO mice (p<0,05), associated with increased levels of inflammatory mediators
in KO mice. These results indicate that C.albicans downregulates the expression of constitutive
mBD1 and inducible mBD14 and this may promote fungal survival in the vaginal niche. While
the systemic role of TLR2 is associated with protective mechanisms, intravaginally activation
would not be relevant to the control of the infection.(Ca) is a common commensal of mucosal surfaces and the most frequent
cause of VVC. Antimicrobial peptides like â-defensins (BDs) are a crucial component of the host
defence at mucosal epithelia. BDs exert antimicrobial and chemoattractant activities. Human
BD1 (mouse BD1 orthologous) is constitutively expressed in normal tissue, while BD3 (mouse
BD14 orthologous) can be induced by inflammation and microorganisms. Herein, we aimed to
study Ca ability to modulate local expression of BDs in mouse models of VVC. Female TLR2-
KO and C57BL/6 wt mice were used. Estrus phase was induced by estradiol injections. Infected
animals (Inf) were intravaginally inoculated with 5.106 Ca ATCC 36801 at day (D) 0. Untreated
uninfected mice were included as controls. At different D of infection, vaginal lavage was
obtained to evaluate fungal burden (CFU) and cytokine levels (ELISA); vaginas were removed
for histological studies (PAS) and RNA analisys. At D2 fungal burden in WT was lower than KO
(p<0,05). IL-1â and IL-6 did not exhibit changes in wt-Inf but an increase of both cytokines was
observed in KO mice (p<0,05). Histological studies showed a major presence of invasive
morphotype in the stratum corneum of KO mice; inflammation was characterized by mild PMNC
infiltration in wt mice and intraepithelial abscesses in KO mice. Expression of mBD1 and mBD14
mRNA transcripts showed disminished levels in wt-Inf animals while KO mice exhibited
increased levels of both BDs (p<0,05). Progression of the infection (D4) revealed major fungal
burden in wt than KO mice (p<0,05), associated with increased levels of inflammatory mediators
in KO mice. These results indicate that C.albicans downregulates the expression of constitutive
mBD1 and inducible mBD14 and this may promote fungal survival in the vaginal niche. While
the systemic role of TLR2 is associated with protective mechanisms, intravaginally activation
would not be relevant to the control of the infection.â-defensins (BDs) are a crucial component of the host
defence at mucosal epithelia. BDs exert antimicrobial and chemoattractant activities. Human
BD1 (mouse BD1 orthologous) is constitutively expressed in normal tissue, while BD3 (mouse
BD14 orthologous) can be induced by inflammation and microorganisms. Herein, we aimed to
study Ca ability to modulate local expression of BDs in mouse models of VVC. Female TLR2-
KO and C57BL/6 wt mice were used. Estrus phase was induced by estradiol injections. Infected
animals (Inf) were intravaginally inoculated with 5.106 Ca ATCC 36801 at day (D) 0. Untreated
uninfected mice were included as controls. At different D of infection, vaginal lavage was
obtained to evaluate fungal burden (CFU) and cytokine levels (ELISA); vaginas were removed
for histological studies (PAS) and RNA analisys. At D2 fungal burden in WT was lower than KO
(p<0,05). IL-1â and IL-6 did not exhibit changes in wt-Inf but an increase of both cytokines was
observed in KO mice (p<0,05). Histological studies showed a major presence of invasive
morphotype in the stratum corneum of KO mice; inflammation was characterized by mild PMNC
infiltration in wt mice and intraepithelial abscesses in KO mice. Expression of mBD1 and mBD14
mRNA transcripts showed disminished levels in wt-Inf animals while KO mice exhibited
increased levels of both BDs (p<0,05). Progression of the infection (D4) revealed major fungal
burden in wt than KO mice (p<0,05), associated with increased levels of inflammatory mediators
in KO mice. These results indicate that C.albicans downregulates the expression of constitutive
mBD1 and inducible mBD14 and this may promote fungal survival in the vaginal niche. While
the systemic role of TLR2 is associated with protective mechanisms, intravaginally activation
would not be relevant to the control of the infection.Ca ability to modulate local expression of BDs in mouse models of VVC. Female TLR2-
KO and C57BL/6 wt mice were used. Estrus phase was induced by estradiol injections. Infected
animals (Inf) were intravaginally inoculated with 5.106 Ca ATCC 36801 at day (D) 0. Untreated
uninfected mice were included as controls. At different D of infection, vaginal lavage was
obtained to evaluate fungal burden (CFU) and cytokine levels (ELISA); vaginas were removed
for histological studies (PAS) and RNA analisys. At D2 fungal burden in WT was lower than KO
(p<0,05). IL-1â and IL-6 did not exhibit changes in wt-Inf but an increase of both cytokines was
observed in KO mice (p<0,05). Histological studies showed a major presence of invasive
morphotype in the stratum corneum of KO mice; inflammation was characterized by mild PMNC
infiltration in wt mice and intraepithelial abscesses in KO mice. Expression of mBD1 and mBD14
mRNA transcripts showed disminished levels in wt-Inf animals while KO mice exhibited
increased levels of both BDs (p<0,05). Progression of the infection (D4) revealed major fungal
burden in wt than KO mice (p<0,05), associated with increased levels of inflammatory mediators
in KO mice. These results indicate that C.albicans downregulates the expression of constitutive
mBD1 and inducible mBD14 and this may promote fungal survival in the vaginal niche. While
the systemic role of TLR2 is associated with protective mechanisms, intravaginally activation
would not be relevant to the control of the infection.6 Ca ATCC 36801 at day (D) 0. Untreated
uninfected mice were included as controls. At different D of infection, vaginal lavage was
obtained to evaluate fungal burden (CFU) and cytokine levels (ELISA); vaginas were removed
for histological studies (PAS) and RNA analisys. At D2 fungal burden in WT was lower than KO
(p<0,05). IL-1â and IL-6 did not exhibit changes in wt-Inf but an increase of both cytokines was
observed in KO mice (p<0,05). Histological studies showed a major presence of invasive
morphotype in the stratum corneum of KO mice; inflammation was characterized by mild PMNC
infiltration in wt mice and intraepithelial abscesses in KO mice. Expression of mBD1 and mBD14
mRNA transcripts showed disminished levels in wt-Inf animals while KO mice exhibited
increased levels of both BDs (p<0,05). Progression of the infection (D4) revealed major fungal
burden in wt than KO mice (p<0,05), associated with increased levels of inflammatory mediators
in KO mice. These results indicate that C.albicans downregulates the expression of constitutive
mBD1 and inducible mBD14 and this may promote fungal survival in the vaginal niche. While
the systemic role of TLR2 is associated with protective mechanisms, intravaginally activation
would not be relevant to the control of the infection.â and IL-6 did not exhibit changes in wt-Inf but an increase of both cytokines was
observed in KO mice (p<0,05). Histological studies showed a major presence of invasive
morphotype in the stratum corneum of KO mice; inflammation was characterized by mild PMNC
infiltration in wt mice and intraepithelial abscesses in KO mice. Expression of mBD1 and mBD14
mRNA transcripts showed disminished levels in wt-Inf animals while KO mice exhibited
increased levels of both BDs (p<0,05). Progression of the infection (D4) revealed major fungal
burden in wt than KO mice (p<0,05), associated with increased levels of inflammatory mediators
in KO mice. These results indicate that C.albicans downregulates the expression of constitutive
mBD1 and inducible mBD14 and this may promote fungal survival in the vaginal niche. While
the systemic role of TLR2 is associated with protective mechanisms, intravaginally activation
would not be relevant to the control of the infection.C.albicans downregulates the expression of constitutive
mBD1 and inducible mBD14 and this may promote fungal survival in the vaginal niche. While
the systemic role of TLR2 is associated with protective mechanisms, intravaginally activation
would not be relevant to the control of the infection.