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Colonization of piglets by <jats:italic>S. suis<\/jats:italic> is very common and occurs early in life. The clinical outcome of infection is influenced by the virulence of the <jats:italic>S. suis<\/jats:italic> strains and the immunity of the animals. Here, the role of innate immunity was studied in cesarean-derived colostrum-deprived piglets inoculated intranasally with either virulent <jats:italic>S. suis<\/jats:italic> strain 10 (S10) or non-virulent <jats:italic>S. suis<\/jats:italic> strain T15. Colonization of the inoculated piglets was confirmed at the end of the study by PCR and immunohistochemistry. Fever (\u226540.5\u00a0\u00b0C) was more prevalent in piglets inoculated with S10 compared to T15 at 4\u00a0h after inoculation. During the 3\u00a0days of monitoring, no other major clinical signs were detected. Accordingly, only small changes in transcription of genes associated with the antibacterial innate immune response were observed at systemic sites, with S10 inducing an earlier response than T15 in blood. Local inflammatory response to the inoculation, evaluated by transcriptional analysis of selected genes in nasal swabs, was more sustained in piglets inoculated with the virulent S10, as demonstrated by transcription of inflammation-related genes, such as <jats:italic>IL1B<\/jats:italic>, <jats:italic>IL1A<\/jats:italic>, and <jats:italic>IRF7<\/jats:italic>. In contrast, most of the gene expression changes in trachea, lungs, and associated lymph nodes were observed in response to the non-virulent T15 strain. Thus, <jats:italic>S. suis<\/jats:italic> colonization in the absence of systemic infection induces an innate immune response in piglets that appears to be related to the virulence potential of the colonizing strain.<\/jats:p>","DOI":"10.1186\/s13567-021-01013-w","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T05:02:38Z","timestamp":1639890158000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Piglet innate immune response to Streptococcus suis colonization is modulated by the virulence of the strain"],"prefix":"10.1186","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7233-2475","authenticated-orcid":false,"given":"Carlos","family":"Neila-Ib\u00e1\u00f1ez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4571-6822","authenticated-orcid":false,"given":"Louise","family":"Brogaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1211-7057","authenticated-orcid":false,"given":"Lola","family":"Pailler-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5246-7276","authenticated-orcid":false,"given":"Jorge","family":"Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1539-7261","authenticated-orcid":false,"given":"Joaquim","family":"Segal\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7489-4882","authenticated-orcid":false,"given":"Mariela","family":"Segura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-4932","authenticated-orcid":false,"given":"Peter M. 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