Transmission plays an important role in establishing pneumococcal colonization. It comprises three key events: shedding to transmit, entering into a susceptible new host, and adhering to the mucosal surface. Shedding of pneumococci from the respiratory tract of a colonized host is a pivotal step in transmission. Using a co-housed littermate mouse model, we evaluated the importance of the susceptibility to colonization of Streptococcus pneumoniae TIGR4 strain shed from index pups to non-colonized naïve contact pups. Despite sufficient pneumococcal shedding from the colonized host, S. pneumoniae was not contagious between littermates. Neutrophils infiltrated the nasal mucosa of contact pups and contributed to susceptibility of pneumococcal colonization during the course of transmission. Rejection of pneumococcal colonization in the contact pups was associated with accumulation of neutrophils in the nasal mucosa. Inflammation, characterized by neutrophil infiltration, prevents newly entering pneumococci from adhering to the respiratory epithelium in contact mice, suggesting that it plays an important role in reducing the rate of transmission in the initial response of naïve susceptible hosts to pneumococcal acquisition. The initial response of contact mice may regulate neutrophil and/or macrophage infiltration and control the acquisition of existing pneumococci.

Department of Otorhinolaryngology Head and Neck Surgery Wakayama Medical University 811 1 Kimiidera Wakayama shi Wakayama 640 8501 Japan

Department of Otorhinolaryngology Tokyo Women's Medical University Medical Center East 2 1 10 Nishiogu Arakawa ku Tokyo 116 0011 Japan

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Adams W, Bhowmick R, Bou Ghanem EN, Wade K, Shchepetov M, Weiser JN, McCormick BA, Tweten RK, Leong JM (2020) Pneumolysin induces 12-lipoxygenase-dependent neutrophil migration during Streptococcus pneumoniae infection. J Immunol 204:101–111. https://doi.org/10.4049/jimmunol.1800748

Bernatoniene J, Zhang Q, Dogan S, Mitchell TJ, Paton JC, Finn A (2008) Induction of CC and CXC chemokines in human antigen-presenting dendritic cells by the pneumococcal proteins pneumolysin and CbpA, and the role played by toll-like receptor 4, NF-kappaB, and mitogen-activated protein kinases. J Infect Dis 198:1823–1833. https://doi.org/10.1086/593177

Das R, LaRose MI, Hergott CB, Leng L, Bucala R, Weiser JN (2014) Macrophage migration inhibitory factor promotes clearance of pneumococcal colonization. J Immunol 193:764–772. https://doi.org/10.4049/jimmunol.1400133

Davis KM, Nakamura S, Weiser JN (2011) Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice. J Clin Invest 121:3666–3676. https://doi.org/10.1172/jci57761

Deniset JF, Surewaard BG, Lee WY, Kubes P (2017) Splenic Ly6G (high) mature and Ly6G (int) immature neutrophils contribute to eradication of S. pneumoniae. J Exp Med 214:1333–1350. https://doi.org/10.1084/jem.20161621

Diavatopoulos DA, Short KR, Price JT, Wilksch JJ, Brown LE, Briles DE, Strugnell RA, Wijburg OL (2010) Influenza A virus facilitates Streptococcus pneumoniae transmission and disease. FASEB J 24:1789–1798. https://doi.org/10.1096/fj.09-146779

Ito M, Hotomi M, Maruyama Y, Hatano M, Sugimoto H, Yoshizaki T, Yamanaka N (2010) Clonal spread of beta-lactamase-producing amoxicillin-clavulanate-resistant (BLPACR) strains of non-typeable Haemophilus influenzae among young children attending a day care in Japan. Int J Pediatr Otorhinolaryngol 74:901–906. https://doi.org/10.1016/j.ijporl.2010.05.008

Jochems SP, Weiser JN, Malley R, Ferreira DM (2017) The immunological mechanisms that control pneumococcal carriage. PLoS Pathog 13:e1006665. https://doi.org/10.1371/journal.ppat.1006665

Kadioglu A, Weiser JN, Paton JC, Andrew PW (2008) The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat Rev Microbiol 6:288–301. https://doi.org/10.1038/nrmicro1871

Kono M, Zafar MA, Zuniga M, Roche AM, Hamaguchi S, Weiser JN (2016) Single cell bottlenecks in the pathogenesis of Streptococcus pneumoniae. PLoS Pathog 12:e1005887. https://doi.org/10.1371/journal.ppat.1005887

Lemon JK, Miller MR, Weiser JN (2015) Sensing of interleukin-1 cytokines during Streptococcus pneumoniae colonization contributes to macrophage recruitment and bacterial clearance. Infect Immun 83:3204–3212. https://doi.org/10.1128/iai.00224-15

Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, Kollis JK, Srivastava A, Lundgren A, Forte S, Thompson CM, Harney KF, Anderson PW, Lipsitch M, Mallay R (2008) Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog 4:e1000159. https://doi.org/10.1371/journal.ppat.1000159

Matthias KA, Roche AM, Standish AJ, Shchepetov M, Weiser JN (2008) Neutrophil-toxin interactions promote antigen delivery and mucosal clearance of Streptococcus pneumoniae. J Immunol 180:6246–6254. https://doi.org/10.4049/jimmunol.180.9.6246

Paudel S, Baral P, Ghimire L, Bergeron S, Jin L, DeCorte JA, Le JT, Cai S, Jeyaseelan S (2019) CXCL1 regulates neutrophil homeostasis in pneumonia-derived sepsis caused by Streptococcus pneumoniae serotype 3. Blood 133:1335–1345. https://doi.org/10.1182/blood-2018-10-878082

Pollenus E, Malengier-Devlies B, Vandermosten L, Pham TT, Mitera T, Possemiers H, Boon L, Opdenakker G, Matthy P, Philippe E, Van den Steen P (2019) Limitations of neutrophil depletion by anti-Ly6G antibodies in two heterogenic immunological models. Immunol Lett 212:30–36. https://doi.org/10.1016/j.imlet.2019.06.006

Richard AL, Siegel SJ, Erikson J, Weiser JN (2014) TLR2 signaling decreases transmission of Streptococcus pneumoniae by limiting bacterial shedding in an infant mouse Influenza A co-infection model. PLoS Pathog 10:e1004339. https://doi.org/10.1371/journal.ppat.1004339

Ritchie ND, Ritchie R, Bayes HK, Mitchell TJ, Evans TJ (2018) IL-17 can be protective or deleterious in murine pneumococcal pneumonia. PLoS Pathog 14:e1007099. https://doi.org/10.1371/journal.ppat.1007099

Shimada J, Yamanaka N, Hotomi M, Suzumoto M, Sakai A, Ubukata K, Mitsuda T, Yokota S, Faden H (2002) Household transmission of Streptococcus pneumoniae among siblings with acute otitis media. J Clin Microbiol 40:1851–1853. https://doi.org/10.1128/jcm.40.5.1851-1853.2002

Short KR, Reading PC, Wang N, Diavatopoulos DA, Wijburg OL (2012) Increased nasopharyngeal bacterial titers and local inflammation facilitate transmission of Streptococcus pneumoniae. mBio 3. https://doi.org/10.1128/mBio.00255-12

Siegel SJ, Tamashiro E, Weiser JN (2015) Clearance of pneumococcal colonization in infants is delayed through altered macrophage trafficking. PLoS Pathog 11:e1005004. https://doi.org/10.1371/journal.ppat.1005004

Siegel SJ, Weiser JN (2015) Mechanisms of bacterial colonization of the respiratory tract. Annu Rev Microbiol 69:425–444. https://doi.org/10.1146/annurev-micro-091014-104209

Steck P, Ritzmann F, Honecker A, Vella G, Herr C, Gaupp R, Bischoff M, Speer T, Tschering T, Bals R, Beisswenger C (2019) Interleukin 17 receptor E (IL-17RE) and IL-17C mediate the recruitment of neutrophils during acute Streptococcus pneumoniae pneumonia. Infect Immun 87. https://doi.org/10.1128/iai.00329-19

Wang W, Zhou A, Zhang X, Xiang Y, Huang Y, Wang L, Zhang S, Liu Y, Yin Y, He Y (2014) Interleukin 17A promotes pneumococcal clearance by recruiting neutrophils and inducing apoptosis through a p38 mitogen-activated protein kinase-dependent mechanism in acute otitis media. Infect Immun 82:2368–2377. https://doi.org/10.1128/iai.00006-14

Weiser JN, Ferreira DM, Paton JC (2018) Streptococcus pneumoniae: transmission, colonization and invasion. Nat Rev Microbiol. 16:355–367. https://doi.org/10.1038/s41579-018-0001-8

Zafar MA, Kono M, Wang Y, Zangari T, Weiser JN (2016) Infant mouse model for the study of shedding and transmission during Streptococcus pneumoniae monoinfection. Infect Immun 84:2714–2722. https://doi.org/10.1128/iai.00416-16

Zafar MA, Hamaguchi S, Zangari T, Cammer M, Weiser JN (2017a) Capsule type and amount affect shedding and transmission of Streptococcus pneumoniae. mBio 8.  https://doi.org/10.1128/mBio.00989-17

Zafar MA, Wang Y, Hamaguchi S, Weiser JN (2017b) Host-to-host transmission of Streptococcus pneumoniae is driven by its inflammatory toxin, pneumolysin. Cell Host Microbe 21:73–83. https://doi.org/10.1016/j.chom.2016.12.005

Zangari T, Wang Y, Weiser JN (2017) Streptococcus pneumoniae transmission is blocked by type-specific immunity in an infant mouse model. mBio 8. https://doi.org/10.1128/mBio.00188-17

Zhang Z, Clarke TB, Weiser JN (2009) Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest 119:1899–1909. https://doi.org/10.1172/jci36731