{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:49:16Z","timestamp":1787500156181,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009229","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>While MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, while interferon stimulated genes (ISGs) were induced along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-\u03baB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, seems central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009229","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T13:32:42Z","timestamp":1621863162000},"page":"e1009229","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are features of alpacas resolving MERS-CoV infection"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-5764","authenticated-orcid":true,"given":"Nigeer","family":"Te","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1032-9091","authenticated-orcid":true,"given":"Jordi","family":"Rodon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5413-4640","authenticated-orcid":true,"given":"Maria","family":"Ballester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1211-7057","authenticated-orcid":true,"given":"Lola","family":"Pailler-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1539-7261","authenticated-orcid":true,"given":"Joaquim","family":"Segal\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7484-444X","authenticated-orcid":true,"given":"J\u00falia","family":"Vergara-Alert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Bensaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"ppat.1009229.ref001","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1056\/NEJMoa1211721","article-title":"Osterhaus ADME, Fouchier RAM. 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Lazear","year":"2019","journal-title":"Immunity. Cell Press"},{"key":"ppat.1009229.ref033","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41564-019-0371-3","article-title":"Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host","author":"M Ahn","year":"2019","journal-title":"Nature Microbiology"},{"key":"ppat.1009229.ref034","doi-asserted-by":"crossref","first-page":"e521","DOI":"10.1016\/S2542-5196(19)30243-8","article-title":"Enzootic patterns of Middle East respiratory syndrome coronavirus in imported African and local Arabian dromedary camels: a prospective genomic study","volume":"3","author":"SA El-Kafrawy","year":"2019","journal-title":"Lancet Planet Heal"},{"key":"ppat.1009229.ref035","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s13337-020-00586-y","article-title":"The dipeptidyl peptidase-4 expression in some MERS-CoV naturally infected dromedary camels in Saudi Arabia 2018\u20132019","volume":"31","author":"A Alnaeem","year":"2020","journal-title":"VirusDisease"},{"key":"ppat.1009229.ref036","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/tbed.13092","article-title":"Co-localization of Middle East respiratory syndrome coronavirus (MERS-CoV) and dipeptidyl peptidase-4 in the respiratory tract and lymphoid tissues of pigs and llamas","author":"N Te","year":"2019","journal-title":"Transboundary and Emerging Diseases"},{"key":"ppat.1009229.ref037","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1172\/JCI126363","article-title":"IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes","volume":"129","author":"R Channappanavar","year":"2019","journal-title":"J Clin Invest"},{"key":"ppat.1009229.ref038","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.33354","article-title":"IFN-\u03bb prevents influenza virus spread from the upper airways to the lungs and limits virus transmission","volume":"7","author":"J Klinkhammer","year":"2018","journal-title":"Elife"},{"key":"ppat.1009229.ref039","first-page":"2143","volume-title":"Journal of Cellular Physiology","author":"S Shokri","year":"2019"},{"key":"ppat.1009229.ref040","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/his.13379","article-title":"Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection\u2014clinicopathological and ultrastructural study","volume":"72","author":"KO Alsaad","year":"2018","journal-title":"Histopathology"},{"key":"ppat.1009229.ref041","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","article-title":"Regulation and Functions of the IL-10 Family of Cytokines in Inflammation and Disease","volume":"29","author":"W Ouyang","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"ppat.1009229.ref042","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/s41590-019-0408-z","article-title":"Interferon-\u03bb modulates 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Verbist","year":"2012","journal-title":"Cytokine"},{"key":"ppat.1009229.ref049","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.4049\/jimmunol.1002720","article-title":"Differential Expression of NLRP3 among Hematopoietic Cells","volume":"186","author":"G Guarda","year":"2011","journal-title":"J Immunol"},{"key":"ppat.1009229.ref050","article-title":"NLRP3 inflammasome and its inhibitors: a review","volume":"6","author":"B-Z Shao","year":"2015","journal-title":"Front Pharmacol."},{"key":"ppat.1009229.ref051","first-page":"2195","volume-title":"Genes and Development","author":"MS Hayden","year":"2004"},{"key":"ppat.1009229.ref052","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1093\/infdis\/jiv392","article-title":"Treatment with lopinavir\/ritonavir or interferon-\u03b21b improves outcome of MERSCoV infection in a nonhuman primate model of common marmoset","volume":"212","author":"JFW Chan","year":"2015","journal-title":"J Infect 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