Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]

Publication Date:
2018-01-09
Publisher:
The American Association of Immunologists (AAI)
Print ISSN:
0022-1767
Electronic ISSN:
1550-6606
Topics:
Medicine
Published by:
_version_ 1836398740899889152
autor Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
beschreibung Numerous studies have reported sex bias in infectious diseases, with bias direction dependent on pathogen and site of infection. Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in susceptibility to S. aureus SSTI has not been described. A search of electronic health records revealed an odds ratio of 2.4 for S. aureus SSTI in males versus females. To investigate the physiological basis of this bias, we compared outcomes between male and female mice in a model of S. aureus dermonecrosis. Consistent with the epidemiological data, female mice were better protected against SSTI, with reduced dermonecrosis followed later by increased bacterial clearance. Protection in females was disrupted by ovariectomy and restored by short-term estrogen administration. Importantly, this sex bias was mediated by a sex-specific response to the S. aureus– secreted virulence factor α-hemolysin (Hla). Infection with wild-type S. aureus suppressed inflammatory cytokine production in the skin of female, but not male, mice when compared with infection with an isogenic hla deletion mutant. This differential response was conserved following injection with Hla alone, demonstrating a direct response to Hla independent of bacterial burden. Additionally, neutrophils, essential for clearing S. aureus , demonstrated sex-specific S. aureus bactericidal capacity ex vivo. This work suggests that sex-specific skin innate responsiveness to Hla and neutrophil bactericidal capacity play important roles in limiting S. aureus SSTI in females. Understanding the molecular mechanisms controlling this sex bias may reveal novel targets to promote host innate defense against S. aureus skin infection.
citation_standardnr 6134059
datenlieferant ipn_articles
feed_id 333
feed_publisher The American Association of Immunologists (AAI)
feed_publisher_url http://www.aai.org/
insertion_date 2018-01-09
journaleissn 1550-6606
journalissn 0022-1767
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association of Immunologists (AAI)
quelle Journal of Immunology
relation http://www.jimmunol.org/cgi/content/short/200/2/657?rss=1
search_space articles
shingle_author_1 Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
shingle_author_2 Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
shingle_author_3 Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
shingle_author_4 Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
shingle_catch_all_1 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
Numerous studies have reported sex bias in infectious diseases, with bias direction dependent on pathogen and site of infection. Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in susceptibility to S. aureus SSTI has not been described. A search of electronic health records revealed an odds ratio of 2.4 for S. aureus SSTI in males versus females. To investigate the physiological basis of this bias, we compared outcomes between male and female mice in a model of S. aureus dermonecrosis. Consistent with the epidemiological data, female mice were better protected against SSTI, with reduced dermonecrosis followed later by increased bacterial clearance. Protection in females was disrupted by ovariectomy and restored by short-term estrogen administration. Importantly, this sex bias was mediated by a sex-specific response to the S. aureus– secreted virulence factor α-hemolysin (Hla). Infection with wild-type S. aureus suppressed inflammatory cytokine production in the skin of female, but not male, mice when compared with infection with an isogenic hla deletion mutant. This differential response was conserved following injection with Hla alone, demonstrating a direct response to Hla independent of bacterial burden. Additionally, neutrophils, essential for clearing S. aureus , demonstrated sex-specific S. aureus bactericidal capacity ex vivo. This work suggests that sex-specific skin innate responsiveness to Hla and neutrophil bactericidal capacity play important roles in limiting S. aureus SSTI in females. Understanding the molecular mechanisms controlling this sex bias may reveal novel targets to promote host innate defense against S. aureus skin infection.
Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_2 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
Numerous studies have reported sex bias in infectious diseases, with bias direction dependent on pathogen and site of infection. Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in susceptibility to S. aureus SSTI has not been described. A search of electronic health records revealed an odds ratio of 2.4 for S. aureus SSTI in males versus females. To investigate the physiological basis of this bias, we compared outcomes between male and female mice in a model of S. aureus dermonecrosis. Consistent with the epidemiological data, female mice were better protected against SSTI, with reduced dermonecrosis followed later by increased bacterial clearance. Protection in females was disrupted by ovariectomy and restored by short-term estrogen administration. Importantly, this sex bias was mediated by a sex-specific response to the S. aureus– secreted virulence factor α-hemolysin (Hla). Infection with wild-type S. aureus suppressed inflammatory cytokine production in the skin of female, but not male, mice when compared with infection with an isogenic hla deletion mutant. This differential response was conserved following injection with Hla alone, demonstrating a direct response to Hla independent of bacterial burden. Additionally, neutrophils, essential for clearing S. aureus , demonstrated sex-specific S. aureus bactericidal capacity ex vivo. This work suggests that sex-specific skin innate responsiveness to Hla and neutrophil bactericidal capacity play important roles in limiting S. aureus SSTI in females. Understanding the molecular mechanisms controlling this sex bias may reveal novel targets to promote host innate defense against S. aureus skin infection.
Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_3 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
Numerous studies have reported sex bias in infectious diseases, with bias direction dependent on pathogen and site of infection. Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in susceptibility to S. aureus SSTI has not been described. A search of electronic health records revealed an odds ratio of 2.4 for S. aureus SSTI in males versus females. To investigate the physiological basis of this bias, we compared outcomes between male and female mice in a model of S. aureus dermonecrosis. Consistent with the epidemiological data, female mice were better protected against SSTI, with reduced dermonecrosis followed later by increased bacterial clearance. Protection in females was disrupted by ovariectomy and restored by short-term estrogen administration. Importantly, this sex bias was mediated by a sex-specific response to the S. aureus– secreted virulence factor α-hemolysin (Hla). Infection with wild-type S. aureus suppressed inflammatory cytokine production in the skin of female, but not male, mice when compared with infection with an isogenic hla deletion mutant. This differential response was conserved following injection with Hla alone, demonstrating a direct response to Hla independent of bacterial burden. Additionally, neutrophils, essential for clearing S. aureus , demonstrated sex-specific S. aureus bactericidal capacity ex vivo. This work suggests that sex-specific skin innate responsiveness to Hla and neutrophil bactericidal capacity play important roles in limiting S. aureus SSTI in females. Understanding the molecular mechanisms controlling this sex bias may reveal novel targets to promote host innate defense against S. aureus skin infection.
Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_4 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
Numerous studies have reported sex bias in infectious diseases, with bias direction dependent on pathogen and site of infection. Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in susceptibility to S. aureus SSTI has not been described. A search of electronic health records revealed an odds ratio of 2.4 for S. aureus SSTI in males versus females. To investigate the physiological basis of this bias, we compared outcomes between male and female mice in a model of S. aureus dermonecrosis. Consistent with the epidemiological data, female mice were better protected against SSTI, with reduced dermonecrosis followed later by increased bacterial clearance. Protection in females was disrupted by ovariectomy and restored by short-term estrogen administration. Importantly, this sex bias was mediated by a sex-specific response to the S. aureus– secreted virulence factor α-hemolysin (Hla). Infection with wild-type S. aureus suppressed inflammatory cytokine production in the skin of female, but not male, mice when compared with infection with an isogenic hla deletion mutant. This differential response was conserved following injection with Hla alone, demonstrating a direct response to Hla independent of bacterial burden. Additionally, neutrophils, essential for clearing S. aureus , demonstrated sex-specific S. aureus bactericidal capacity ex vivo. This work suggests that sex-specific skin innate responsiveness to Hla and neutrophil bactericidal capacity play important roles in limiting S. aureus SSTI in females. Understanding the molecular mechanisms controlling this sex bias may reveal novel targets to promote host innate defense against S. aureus skin infection.
Castleman, M. J., Pokhrel, S., Triplett, K. D., Kusewitt, D. F., Elmore, B. O., Joyner, J. A., Femling, J. K., Sharma, G., Hathaway, H. J., Prossnitz, E. R., Hall, P. R.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_title_1 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
shingle_title_2 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
shingle_title_3 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
shingle_title_4 Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
timestamp 2025-06-30T23:31:53.823Z
titel Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
titel_suche Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by {alpha}-Hemolysin [INFECTIOUS DISEASE AND HOST RESPONSE]
topic WW-YZ
uid ipn_articles_6134059