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APP-induced piglet respiratory disease complex (PRDC) is highly prevalent in winter and triggers an intense inflammatory response in the lungs at disease onset, accompanied by severe infiltration of porcine alveolar macrophages (PAMs). The magnitude of the PAM-mediated immune response following APP infection is a key factor influencing the regression of respiratory disease. However, it remains unclear whether cold stimulation exacerbates this response. In this study, we found that cold stimulation exacerbated APP-induced lung injury and enhanced macrophage activation. Metabolomics and transcriptomics analyses revealed that immune cells underwent metabolic reprogramming in response to energy mobilisation after APP infection, thereby interfering with lung immune function. In addition, we identified silent information regulator 2 (SIRT2) as a key regulator of PAM activation and demonstrated at the molecular level that SIRT2 mediates the immune response to PAMs following APP infection by regulating the acetylation modification of NF-\u03baB p65. In conclusion, our results elucidate the role of SIRT2 in regulating the immune response to PAMs in piglets infected with APP under low-temperature conditions. These findings may provide potential intervention targets and effective control pathways to address the overactivity of immune cells induced by environmental stress and reduce the high incidence of winter respiratory disease in piglets.\n                  <\/jats:p>","DOI":"10.1186\/s13567-026-01780-4","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T11:39:36Z","timestamp":1781437176000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms by which SIRT2 modulates alveolar macrophage immunoreactivity to intervene in Actinobacillus pleuropneumoniae infection in piglets under cold stimulation"],"prefix":"10.1186","volume":"57","author":[{"given":"Rongge","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqun","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinpeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boxi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9395-3606","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"1780_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10091202","volume":"10","author":"F Vangroenweghe","year":"2021","unstructured":"Vangroenweghe F, Thas O (2021) Seasonal variation in prevalence of Mycoplasma hyopneumoniae and other respiratory pathogens in peri-weaned, post-weaned, and fattening pigs with clinical signs of respiratory diseases in Belgian and Dutch pig herds, using a tracheobronchial swab sampling technique, and their associations with local weather conditions. 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