IFN-γ plays a detrimental role in murine defense against nasal colonization of Staphylococcus aureus

Satorres, Sara Elena; Alcaráz, Lucía Esther; Cargnelutti, Ethelina; Genaro, María Silvia Di

doi:10.1016/j.imlet.2009.03.003

Cited by 18 publications

(14 citation statements)

References 24 publications

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“…Neutralization of IFN-␥ improved protection in C57BL/6 mice, whereas neutralization of IL-17A abrogated protection in BALB/c mice. Therefore, our observations are consistent with recent reports that the Th17/IL-17 pathway is protective and that Th1/IFN-␥ responses are deleterious (14,(27)(28)(29)(30)(31). However, our observations suggest that the ratio of the Th17 responses to Th1 responses rather than the magnitude of the Th17 response per se determines protection and that this ratio of T cell responses is determined by the genetic background of the infected host.…”

Section: Discussionsupporting

confidence: 92%

Protective Immunity against Recurrent Staphylococcus aureus Skin Infection Requires Antibody and Interleukin-17A

et al. 2014

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Although many microbial infections elicit an adaptive immune response that can protect against reinfection, it is generally thought that Staphylococcus aureus infections fail to generate protective immunity despite detectable T and B cell responses. No vaccine is yet proven to prevent S. aureus infections in humans, and efforts to develop one have been hampered by a lack of animal models in which protective immunity occurs. Our results describe a novel mouse model of protective immunity against recurrent infection, in which S. aureus skin and soft tissue infection (SSTI) strongly protected against secondary SSTI in BALB/c mice but much less so in C57BL/6 mice. This protection was dependent on antibody, because adoptive transfer of immune BALB/c serum or purified antibody into either BALB/c or C57BL/6 mice resulted in smaller skin lesions. We also identified an antibody-independent mechanism, because B cell-deficient mice were partially protected against secondary S. aureus SSTI and adoptive transfer of T cells from immune BALB/c mice resulted in smaller lesions upon primary infection. Furthermore, neutralization of interleukin-17A (IL-17A) abolished T cell-mediated protection in BALB/c mice, whereas neutralization of gamma interferon (IFN-␥) enhanced protection in C57BL/6 mice. Therefore, protective immunity against recurrent S. aureus SSTI was advanced by antibody and the Th17/IL-17A pathway and prevented by the Th1/IFN-␥ pathway, suggesting that targeting both cell-mediated and humoral immunity might optimally protect against secondary S. aureus SSTI. These findings also highlight the importance of the mouse genetic background in the development of protective immunity against S. aureus SSTI.

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Section: Discussionsupporting

confidence: 92%

Protective Immunity against Recurrent Staphylococcus aureus Skin Infection Requires Antibody and Interleukin-17A

et al. 2014

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“…The involvement of pro-inflammatory cytokines in the pathogenesis of S. aureus infection has been reported. This bacteria can induce cytokines such as TNF-α, IFN-γ, IL-1, IL-2, and IL-6 [6,7]. Cytokines released from macrophages as TNF-α, IL-1β and IL-6 have been classically pointed as the major players of the severe inflammation that precedes cartilage and bone destruction in SA [2].…”

Section: Introductionmentioning

confidence: 99%

Differential arthritogenicity of Staphylococcus aureusstrains isolated from biological samples

et al. 2013

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BackgroundStaphylococcus aureus is the most common agent of septic arthritis that is a severe, rapidly progressive and destructive joint disease. Superantigens produced by S. aureus are considered the major arthritogenic factors. In this study, we compared the arthritogenic potential of five superantigen-producing staphylococcal strains.MethodsMale C57BL/6 mice were intravenously infected with ATCC 19095 SEC+, N315 ST5 TSST-1+, S-70 TSST-1+, ATCC 51650 TSST-1+ and ATCC 13565 SEA+ strains. Clinical parameters as body weight, arthritis incidence and clinical score were daily evaluated. Joint histopathological analysis and spleen cytokine production were evaluated at the 14th day after infection.ResultsWeight loss was observed in all infected mice. ATCC 19095 SEC+, N315 ST5 TSST-1+ and S-70 TSST-1+ were arthritogenic, being the highest scores observed in ATCC 19095 SEC+ infected mice. Intermediate and lower clinical scores were observed in N315 ST5 TSST-1+ and S-70 TSST-1+ infected mice, respectively. The ATCC 13565 SEA+ strain caused death of 85% of the animals after 48 h. Arthritis triggered by the ATCC 19095 SEC+ strain was characterized by accentuated synovial hyperplasia, inflammation, pannus formation, cartilage destruction and bone erosion. Similar joint alterations were found in N315 ST5 TSST-1+ infected mice, however they were strikingly more discrete. Only minor synovial proliferation and inflammation were triggered by the S-70 TSST-1+ strain. The lowest levels of TNF-α, IL-6 and IL-17 production in response to S. aureus stimulation were found in cultures from mice infected with the less arthritogenic strains (S-70 TSST-1+ and ATCC 51650 TSST-1+). The highest production of IL-17 was detected in mice infected with the most arthritogenic strains (ATCC 19095 SEC+ and N315 ST5 TSST-1+).ConclusionsTogether these results demonstrated that S. aureus strains, isolated from biological samples, were able to induce a typical septic arthritis in mice. These results also suggest that the variable arthritogenicity of these strains was, at least in part, related to their differential ability to induce IL-17 production.

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“…The importance of IL-12 during bacterial infections has been extensively investigated (11)(12)(13)24), including in S. aureus bacterial colonization (16,17) and S. aureus-induced brain abscesses (15). In the two cases, IL-12 was found to be either nonprotective or actually detrimental for resistance to S. aureus infection.…”

Section: Discussionmentioning

confidence: 99%

“…However, while IL-12 expression can be induced during S. aureus infection (14), appears to play a more dominant role in staphylococcal infections and IL-12 is nonprotective, at least for acute disease involving brain abscesses and cutaneous infections (15,16). In fact, it has been reported that IL-12 and IFN-␥ are detrimental for controlling staphylococcal colonization (17) and for recovery from central nervous system (CNS) bacterial-induced inflammation (15). Nevertheless, IFN-␥ is routinely given to patients with chronic granulomatous disease who have particular difficulty in killing S. aureus (but not S. pneumoniae).…”

mentioning

confidence: 99%

Role of Interleukin-12 in Protection against Pulmonary Infection with Methicillin-Resistant Staphylococcus aureus

Nguyen

Furuya

Roberts

et al. 2015

Antimicrob Agents Chemother

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IFN-γ plays a detrimental role in murine defense against nasal colonization of Staphylococcus aureus

Cited by 18 publications

References 24 publications

Protective Immunity against Recurrent Staphylococcus aureus Skin Infection Requires Antibody and Interleukin-17A

Protective Immunity against Recurrent Staphylococcus aureus Skin Infection Requires Antibody and Interleukin-17A

Differential arthritogenicity of Staphylococcus aureusstrains isolated from biological samples

Role of Interleukin-12 in Protection against Pulmonary Infection with Methicillin-Resistant Staphylococcus aureus

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