HLA-DQ8 transgenic mice lacking endogenous class II molecules respond to house dust allergens: identification of antigenic epitopes.

Neeno, Teresa; Krco, Christopher J.; Harders, Jerry; Baisch, Jeanine; Cheng, Shen; David, Chella S.

doi:10.4049/jimmunol.156.9.3191

Cited by 26 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HLA-II-expressing humanized mouse models are well-established and frequently used as clinical translation models for studying mechanisms underlying dysregulated host immune responses to infections [ 10 , 20 , 21 ], streptococcal and staphylococcal superantigen responses, dermatitis, collagen-induced arthritis [ 22 , 23 , 24 ], food allergens [ 25 ], dust allergens [ 26 ], progression of demyelination and neurological deficits in Theiler’s murine encephalomyelitis virus infection [ 27 ], and brain pathology in experimental autoimmune encephalomyelitis [ 28 , 29 ]. Building upon our previous work [ 30 ], and given the potential for the differential presentation of immune responses and outcomes by DR and DQ alleles, in the present study, we utilized the HLA-DQ8 (DQA1*0301/DQB1*0302) mice (DQ8) to investigate the skin–brain axis and effects of clindamycin (CLN) following subcutaneous GAS infection.…”

Section: Introductionmentioning

confidence: 99%

Concurrent Brain Subregion Microgliosis in an HLA-II Mouse Model of Group A Streptococcal Skin Infection

Nookala,

Mukundan,

Grove

et al. 2023

Microorganisms

View full text Add to dashboard Cite

The broad range of clinical manifestations and life-threatening infections caused by the Gram-positive bacterium, Streptococcus pyogenes or Group A Streptococcus (GAS), remains a significant concern to public health, with a subset of individuals developing neurological complications. Here, we examined the concurrent neuroimmune effects of subcutaneous GAS infections in an HLA-Class II (HLA) transgenic mouse model of subcutaneous GAS infection. To investigate changes in the skin–brain axis, HLA-DQ8 (DQA1*0301/DQB1*0302) mice (DQ8) were randomly divided into three groups: uninfected controls (No Inf), GAS infected and untreated (No Tx), and GAS infected with a resolution by clindamycin (CLN) treatment (CLN Tx) (10 mg/kg/5 days) and were monitored for 16 days post-infection. While the skin GAS burden was significantly reduced by CLN, the cortical and hippocampal GAS burden in the male DQ8 mice was not significantly reduced with CLN. Immunoreactivity to anti-GAS antibody revealed the presence of GAS bacteria in the vicinity of the neuronal nucleus in the neocortex of both No Tx and CLN Tx male DQ8 mice. GAS infection-mediated cortical cytokine changes were modest; however, compared to No Inf or No Tx groups, a significant increase in IL-2, IL-13, IL-22, and IL-10 levels was observed in CLN Tx females despite the lack of GAS burden. Western blot analysis of cortical and hippocampal homogenates showed significantly higher ionized calcium-binding adaptor-1 (Iba-1, microglia marker) protein levels in No Tx females and males and CLN Tx males compared to the No Inf group. Immunohistochemical analysis showed that Iba-1 immunoreactivity in the hippocampal CA3 and CA1 subregions was significantly higher in the CLN Tx males compared to the No Tx group. Our data support the possibility that the subcutaneous GAS infection communicates to the brain and is characterized by intraneuronal GAS sequestration, brain cytokine changes, Iba-1 protein levels, and concurrent CA3 and CA1 subregion-specific microgliosis, even without bacteremia.

show abstract

Section: Introductionmentioning

confidence: 99%

Concurrent Brain Subregion Microgliosis in an HLA-II Mouse Model of Group A Streptococcal Skin Infection

Nookala,

Mukundan,

Grove

et al. 2023

Microorganisms

View full text Add to dashboard Cite

show abstract

Cellular Mechanisms of Target Antigen Attack in Experimental Autoimmune Myasthenia Gravis

Poussin

Christadoss

2000

Myasthenia Gravis

View full text Add to dashboard Cite

Preclinical Models Used for Immunogenicity Prediction of Therapeutic Proteins

Brinks

Weinbuch

Baker³

et al. 2013

Pharm Res

View full text Add to dashboard Cite

All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to predict immunogenicity of drug leads, to modify potentially immunogenic properties and to continue development of drug candidates with expected low immunogenicity. Despite the extensive use of these predictive models, their actual predictive value varies. Important reasons for this uncertainty are the limited/insufficient knowledge on the immune mechanisms underlying immunogenicity of therapeutic proteins, the fact that different predictive models explore different components of the immune system and the lack of an integrated clinical validation. In this review, we discuss the predictive models in use, summarize aspects of immunogenicity that these models predict and explore the merits and the limitations of each of the models.

show abstract

HLA-DQ8 transgenic mice lacking endogenous class II molecules respond to house dust allergens: identification of antigenic epitopes.

Cited by 26 publications

References 0 publications

Concurrent Brain Subregion Microgliosis in an HLA-II Mouse Model of Group A Streptococcal Skin Infection

Concurrent Brain Subregion Microgliosis in an HLA-II Mouse Model of Group A Streptococcal Skin Infection

Cellular Mechanisms of Target Antigen Attack in Experimental Autoimmune Myasthenia Gravis

Preclinical Models Used for Immunogenicity Prediction of Therapeutic Proteins

Contact Info

Product

Resources

About