Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens
Resiquimod (R-848), a synthetic TLR7 agonist, modulates immune responses, primarily inducing Th1-biased immunity in mammals. In contrast, our previous studies revealed that R-848 stimulates both Th1 and Th2 responses in chickens. The current research investigates the molecular mechanisms underlying...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | Biochemistry and Biophysics Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825000287 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540426755637248 |
|---|---|
| author | Deepthi Kappala Saravanan Ramakrishnan Patel Nikunjkumar Prakashbhai Abinaya Kaliappan Prasad Thomas Jörg Linde Mithilesh Singh Sohini Dey Madhan Mohan Chellappa |
| author_facet | Deepthi Kappala Saravanan Ramakrishnan Patel Nikunjkumar Prakashbhai Abinaya Kaliappan Prasad Thomas Jörg Linde Mithilesh Singh Sohini Dey Madhan Mohan Chellappa |
| author_sort | Deepthi Kappala |
| collection | DOAJ |
| description | Resiquimod (R-848), a synthetic TLR7 agonist, modulates immune responses, primarily inducing Th1-biased immunity in mammals. In contrast, our previous studies revealed that R-848 stimulates both Th1 and Th2 responses in chickens. The current research investigates the molecular mechanisms underlying these immune responses in chickens. Pooled splenocytes harvested from chickens (n = 2/group) at 24 h post R-848 treatment were subjected to RNA sequencing and significant differentially expressed genes (DEGs) were identified compared to controls. Eight key genes associated with signal transduction (MAPK14, MAP3K8, PIK3CD, STAT1, STAT3, MAPK11, LRRK2, and GATA3) were validated via real-time PCR in chicken peripheral blood mononuclear cells (PBMCs) from six biological replicates. Pharmacological inhibitors or chloroquine were employed to elucidate the signalling pathways. SB202190, IC-87114, and fludarabine phosphate suppressed the R-848-induced expression of MAPK14, PIK3CD, and STAT1, respectively, while chloroquine decreased STAT3 expression. Intriguingly, chloroquine treatment enhanced the R-848-mediated expression of MAPK11, LRRK2, and GATA3. These results align with transcriptomic findings and highlight the upregulation of STAT1 and STAT3 as potential contributors to the induction of Th1 and Th2 immune responses by R-848 in chickens. These insights provide a foundation for optimizing R-848 as an immunomodulatory agent in avian species. |
| format | Article |
| id | doaj-art-ddc12e18d4b349208a208f217dced2d4 |
| institution | Kabale University |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-ddc12e18d4b349208a208f217dced2d42025-02-05T04:32:14ZengElsevierBiochemistry and Biophysics Reports2405-58082025-03-0141101941Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickensDeepthi Kappala0Saravanan Ramakrishnan1Patel Nikunjkumar Prakashbhai2Abinaya Kaliappan3Prasad Thomas4Jörg Linde5Mithilesh Singh6Sohini Dey7Madhan Mohan Chellappa8Immunology Section, ICAR - Indian Veterinary Research Institute, Bareilly, IndiaImmunology Section, ICAR - Indian Veterinary Research Institute, Bareilly, India; Corresponding author.Immunology Section, ICAR - Indian Veterinary Research Institute, Bareilly, IndiaImmunology Section, ICAR - Indian Veterinary Research Institute, Bareilly, IndiaDivision of Bacteriology and Mycology, ICAR - Indian Veterinary Research Institute, Bareilly, IndiaInstitute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut, Jena, GermanyImmunology Section, ICAR - Indian Veterinary Research Institute, Bareilly, IndiaRecombinant DNA Laboratory, Division of Veterinary Biotechnology, ICAR - Indian Veterinary Research Institute, Bareilly, IndiaRecombinant DNA Laboratory, Division of Veterinary Biotechnology, ICAR - Indian Veterinary Research Institute, Bareilly, IndiaResiquimod (R-848), a synthetic TLR7 agonist, modulates immune responses, primarily inducing Th1-biased immunity in mammals. In contrast, our previous studies revealed that R-848 stimulates both Th1 and Th2 responses in chickens. The current research investigates the molecular mechanisms underlying these immune responses in chickens. Pooled splenocytes harvested from chickens (n = 2/group) at 24 h post R-848 treatment were subjected to RNA sequencing and significant differentially expressed genes (DEGs) were identified compared to controls. Eight key genes associated with signal transduction (MAPK14, MAP3K8, PIK3CD, STAT1, STAT3, MAPK11, LRRK2, and GATA3) were validated via real-time PCR in chicken peripheral blood mononuclear cells (PBMCs) from six biological replicates. Pharmacological inhibitors or chloroquine were employed to elucidate the signalling pathways. SB202190, IC-87114, and fludarabine phosphate suppressed the R-848-induced expression of MAPK14, PIK3CD, and STAT1, respectively, while chloroquine decreased STAT3 expression. Intriguingly, chloroquine treatment enhanced the R-848-mediated expression of MAPK11, LRRK2, and GATA3. These results align with transcriptomic findings and highlight the upregulation of STAT1 and STAT3 as potential contributors to the induction of Th1 and Th2 immune responses by R-848 in chickens. These insights provide a foundation for optimizing R-848 as an immunomodulatory agent in avian species.http://www.sciencedirect.com/science/article/pii/S2405580825000287ResiquimodToll-like receptor signallingChickenTh1 and Th2 immune responsesTranscriptomic profile |
| spellingShingle | Deepthi Kappala Saravanan Ramakrishnan Patel Nikunjkumar Prakashbhai Abinaya Kaliappan Prasad Thomas Jörg Linde Mithilesh Singh Sohini Dey Madhan Mohan Chellappa Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens Biochemistry and Biophysics Reports Resiquimod Toll-like receptor signalling Chicken Th1 and Th2 immune responses Transcriptomic profile |
| title | Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens |
| title_full | Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens |
| title_fullStr | Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens |
| title_full_unstemmed | Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens |
| title_short | Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens |
| title_sort | resiquimod induces a mixed th1 and th2 response via stat1 and stat3 signalling in chickens |
| topic | Resiquimod Toll-like receptor signalling Chicken Th1 and Th2 immune responses Transcriptomic profile |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825000287 |
| work_keys_str_mv | AT deepthikappala resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens AT saravananramakrishnan resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens AT patelnikunjkumarprakashbhai resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens AT abinayakaliappan resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens AT prasadthomas resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens AT jorglinde resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens AT mithileshsingh resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens AT sohinidey resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens AT madhanmohanchellappa resiquimodinducesamixedth1andth2responseviastat1andstat3signallinginchickens |