1. Yániz J, Capistrós S, Vicente-Fiel S, Hidalgo C, Santolaria P. A comparative study of the morphometry of sperm head components in cattle, sheep, and pigs with a computer-assisted fluorescence method. Asian J Androl. 2016;18:840–3.
2. Atkinson BA, King GJ, Amoroso EC. Development of the caruncular and intercaruncular regions in the bovine endometrium. Biol Reprod. 1984;30:763–74.
3. Gray CA, Bartol FF, Tarleton BJ, Wiley AA, Johnson GA, Bazer FW, et al. Developmental Biology of Uterine Glands1. Biol Reprod. 2001;65:1311–23.
4. Wimsatt WA. New histological observations on the placenta of the sheep. Am J Anat. 1950;87:391–457.
5. Bazer FW. Uterine Protein Secretions: Relationship to Development of the Conceptus. J Anim Sci. 1975;41:1376–82.
6. Dhaliwal GS, Murray RD, Rees EM, Howard C V., Beech DJ. Quantitative unbiased estimates of endometrial gland surface area and volume in cycling cows and heifers. Res Vet Sci. 2002;73:259– 65.
7. O’Shea JD, Wright PJ. Involution and regeneration of the endometrium following parturition in the ewe. Cell Tissue Res. 1984;236:477–85.
8. Ohtani S, Okuda K, Nishimura K, Mohri S. Histological changes in bovine endometrium during the estrous cycle. Theriogenology. 1993;39:1033–42.
9. Wang CK, Robinson RS, Flint APF, Mann GE. Quantitative analysis of changes in endometrial gland morphology during the bovine oestrous cycle and their association with progesterone levels. Reproduction. 2007;134:365–71.
10. Sobrero AJ, Macleod J. The immediate postcoital test. Fertil Steril. 1962;13:184–9. doi:10.1016/s0015-0282(16)34447-8.
11. Bedford JM, Yanagimachi R. Initiation of Sperm Motility after Mating in the Rat and Hamster. Journal of Andrology. 1992;13:444–9.
12. Mitchell JR, Senger PL, Rosenberger JL. Distribution and retention of spermatozoa with acrosomal and nuclear abnormalities in the cow genital tract. J Anim Sci. 1985;61:956–67.
13. Hunter RH. Sperm transport and reservoirs in the pig oviduct in relation to the time of ovulation. J Reprod Fertil. 1981;63:109–17.
14. Mattner PE. The distribution of spermatozoa and leucocytes in the female genital tract in goats and cattle. J Reprod Fertil. 1968;17:253–61.
15. Hawk HW. Transport and fate of spermatozoa after insemination of cattle. J Dairy Sci. 1987;70:1487–503.
16. Pretorius E, Franken DR, De Wet J, Grobler S. Sperm selection capacity of cervical mucus. Arch Androl. 1984;12:5–7.
17. N. L. First, R. E. Short, J. B. Peters FWS. Transport and Loss of Boar Spermatozoa in the Reproductive Tract of the Sow. J Anim Sci. 1968;27:1037–40.
18. Lovell JW, Getty R. Fate of semen in the uterus of the sow: histologic study of endometrium during the 27 hours after natural service. Am J Vet Res. 1968;29:609–25.
19. Taylor U, Rath D, Zerbe H, Schuberth HJ. Interaction of intact porcine spermatozoa with epithelial cells and neutrophilic granulocytes during uterine passage. Reprod Domest Anim. 2008;43:166–75.
20. Suga T, Higaki S. Studies on uterine secretions in the cow. II. Distribution of spermatozoa and seminal plasma after intra-uterine inseminations in the reproductive tract of the cow during oestrus. Bull Natl Inst Anim Ind. 1971;24:41–8.
21. Fusi FM, Vigano P, Daverio R, Busacca M VM. Effects of the coculture with human endometrial cells on the function of spermatozoa from subfertile men. Fertil Steril. 1994;61:160–7.
22. Pursel VG, Schulman LL, Johnson LA. Distribution and Morphology of Fresh and Frozen-Thawed Sperm in the Reproductive Tract of Gilts after Artificial Insemination. Biol Reprod. 1978;19:69– 76.
23. Kotilainen T, Huhtinen M, Katila T. Sperm-induced leukocytosis in the equine uterus. Theriogenology. 1994;41:629–36.
24. Elweza AE, Ezz MA, Acosta TJ, Talukder AK, Shimizu T, Hayakawa H, et al. A proinflammatory response of bovine endometrial epithelial cells to active sperm in vitro. Mol Reprod Dev. 2018;85:215–26.
25. Austin CR. Fate of spermatozoa in the female genital tract of domestic animals. J Reprod Fertil. 1960;1:151–6.
26. Doak RL, Hall A, Dale HE. Longevity of spermatozoa in the reproductive tract of the bitch. J Reprod Fertil. 1967;13:51–8.
27. Koyama H, Tsutsumi Y, Suzuki H. Observations on Sperm Penetration into the Uterine Gland of the Rabbit, Sow and Cow. Jpn J Zootech Sci. 1986;57:512–23.
28. Racey PA, Uchida TA, Mori T, Avery MI, Fenton MB. Sperm-epithelium relationships in relation to the time of insemination in little brown bats (Myotis lucifugus). J Reprod Fertil. 1987;80:445– 54.
29. England GCW, Burgess CM, Freeman SL, Smith SC, Pacey AA. Relationship between the fertile period and sperm transport in the bitch. Theriogenology. 2006;66:1410–8.
30. Rijsselaere T, Van Soom A, Van Cruchten S, Coryn M, Görtz K, Maes D, et al. Sperm distribution in the genital tract of the bitch following artificial insemination in relation to the time of ovulation. Reproduction. 2004;128:801–11.
31. Karre I, Meyer-Lindenberg A, Urhausen C, Beineke A, Meinecke B, Piechotta M, et al. Distribution and viability of spermatozoa in the canine female genital tract during post-ovulatory oocyte maturation. Acta Vet Scand. 2012;54:49.
32. Mattner PE, Braden AW. Comparison of the distribution of motile and immotile spermatozoa in the ovine cervix. Aust J Biol Sci. 1969;22:1069–70.
33. Suarez SS, Pacey AA. Sperm transport in the female reproductive tract. Hum Reprod Update. 2006;12:23–37.
34. Suarez SS, Brockman K, Lefebvre R. Distribution of Mucus and Sperm in Bovine Oviducts after Artificial Insemination : The Physical Environment of the Oviductal Sperm Reservoir ’. Biol Reprod. 1997;56:447–53.
35. Suarez SS. Mammalian sperm interactions with the female reproductive tract. Cell Tissue Res. 2016;363:185–94.
36. Lefebvre R, Chenoweth PJ, Drost M, LeClear CT, MacCubbin M, Dutton JT, et al. Characterization of the oviductal sperm reservoir in cattle. Biol Reprod. 1995;53:1066–74.
37. Pollard JW, Plante C, King WA, Hansen PJ, Betteridge KJ, Suarez SS. Fertilizing capacity of bovine sperm may be maintained by binding of oviductal epithelial cells. Biol Reprod. 1991;44:102–7.
38. Chang H, Suarez SS. Unexpected flagellar movement patterns and epithelial binding behavior of mouse sperm in the oviduct. Biol Reprod. 2012;86:140, 1–8.
39. Lefebvre R, Suarez SS. Effect of capacitation on bull sperm binding to homologous oviductal epithelium. Biol Reprod. 1996;54:575–82.
40. Wira CR, Fahey J V., Sentman CL, Pioli PA, Shen L. Innate and adaptive immunity in female genital tract: Cellular responses and interactions. Immunol Rev. 2005;206:306–35.
41. Sheldon IM, Cronin JG, Healey GD, Gabler C, Heuwieser W, Streyl D, et al. Innate immunity and inflammation of the bovine female reproductive tract in health and disease. Reproduction. 2014;148.
42. Amjadi F, Salehi E, Mehdizadeh M, Aflatoonian R. Role of the innate immunity in female reproductive tract. Adv Biomed Res. 2014;3:1.
43. Schuberth HJ, Taylor U, Zerbe H, Waberski D, Hunter R, Rath D. Immunological responses to semen in the female genital tract. Theriogenology. 2008;70:1174–81.
44. Hansen PJ. The Immunology of Early Pregnancy in Farm Animals. Reprod Domest Anim. 2011;46 SUPPL. 3:18–30.
45. Robertson SA. Seminal fluid signaling in the female reproductive tract: lessons from rodents and pigs. J Anim Sci. 2007;85 13 Suppl:E36-44.
46. Hahn S, Giaglis S, Hoesli I, Hasler P, Yost CC, Hermesch AC. Neutrophil NETs in reproduction : from infertility to preeclampsia and the possibility of fetal loss. Front Immunol. 2012;3 November:1–8.
47. Kaeoket K, Persson E, Dalin A-M. Corrigendum to “The sow endometrium at different stages of the oestrus cycle: studies on morphological changes and infiltration by cells of the immune system.” [Anim. Reprod. Sci. 65 (2001) 95-114]. Anim Reprod Sci. 2002;73:89–107.
48. Kaeoket K, Persson E, Dalin A-M. Influence of pre-ovulatory insemination and early pregnancy on the distribution of CD2, CD4, CD8 and MHC class II expressing cells in the sow endometrium. Anim Reprod Sci. 2003;76:231–44.
49. Katila T. Post-mating Inflammatory Responses of the Uterus. Reprod Domest Anim. 2012;47 SUPPL. 5:31–41.
50. Pandya IJ, Cohen J. The leukocytic reaction of the human uterine cervix to spermatozoa. Fertility and Sterility. 1985;43:417–21.
51. Tyler KR. Histological changes in the cervix of the rabbit after coitus. Journal of Reproduction and Fertility. 1977;49:341–5.
52. Rozeboom KJ, Troedsson MH, Crabo BG. Characterization of uterine leukocyte infiltration in gilts after artificial insemination. J Reprod Fertil. 1998;114:195–9.
53. Phillips DM, Mahler S. Leukocyte emigration and migration in the vagina following mating in the rabbit. Anat Rec. 1977;189:45–59.
54. Austin CR. Fate of Spermatozoa in the uterus of the mouse and rat. J Endocrinol. 1957;14:335-NP.
55. England GCW, Russo M, Freeman SL. The bitch uterine response to semen deposition and its modification by male accessory gland secretions. Vet J. 2013;195:179–84.
56. Katila T. Onset and Duration of Uterine Inflammatory Response of Mares after Insemination with Fresh Semen. Biol Reprod. 1995;52 monograph_series1:515–7.
57. Rodriguez-Martinez H, Saravia F, Wallgren M, Martinez EA, Sanz L, Roca J, et al. Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow. J Reprod Immunol. 2010;84:57–65.
58. Howe GR, Black DL. Spermatozoan Transport and Leucocytic Responses in the Reproductive Tract of Calves. J Reprod Fertil. 1963;6:305–11.
59. Alghamdi AS, Lovaas BJ, Bird SL, Lamb GC, Rendahl AK, Taube PC, et al. Species-specific interaction of seminal plasma on sperm–neutrophil binding. Anim Reprod Sci. 2009;114:331–44.
60. Troedsson MHT, Loset K, Alghamdi AM, Dahms B, Crabo BG. Interaction between equine semen and the endometrium: The inflammatory response to semen. Anim Reprod Sci. 2001;68:273–8.
61. Bedford JM. Effect of environment on phagocytosis of rabbit spermatozoa. Reproduction. 1965;9:249–56.
62. Dobrowolski W, Hafez ESE. Transport and Distribution of Spermatozoa in the Reproductive tract of the Cow. J Anim Sci. 1970;31:940–3.
63. Wang XL, Liu HR, Tao L, Liang F, Yan L, Zhao RR, et al. Role of iNOS-derived reactive nitrogen species and resultant nitrative stress in leukocytes-induced cardiomyocyte apoptosis after myocardial ischemia/reperfusion. Apoptosis. 2007;12:1209–17.
64. Vogelpoel FR, Verhoef J. Activation of polymorphonuclear leukocytes by spermatozoa. Arch Androl. 1985;14:123–31.
65. Matthijs A, Harkema W, Engel B, Woelders H. In vitro phagocytosis of boar spermatozoa by neutrophils from peripheral blood of sows. J Reprod Fertil. 2000;120:265–73.
66. Matthijs A, Engel B, Woelders H. Neutrophil recruitment and phagocytosis of boar spermatozoa after artificial insemination of sows, and the effects of inseminate volume, sperm dose and specific additives in the extender. Reproduction. 2003;125:357–67.
67. O’Leary S, Jasper MJ, Warnes GM, Armstrong DT, Robertson SA. Seminal plasma regulates endometrial cytokine expression, leukocyte recruitment and embryo development in the pig. Reproduction. 2004;128:237–47.
68. Palm F, Walter I, Budik S, Kolodziejek J, Nowotny N, Aurich C. Influence of different semen extenders and seminal plasma on PMN migration and on expression of IL-1β, IL-6, TNF-α and COX-2 mRNA in the equine endometrium. Theriogenology. 2008;70:843–51.
69. Taylor U, Zerbe H, Seyfert HM, Rath D, Baulain U, Langner KFA, et al. Porcine spermatozoa inhibit post-breeding cytokine induction in uterine epithelial cells in vivo. Anim Reprod Sci. 2009;115:279–89.
70. Fumuso EA, Aguilar J, Giguère S, Rivulgo M, Wade J, Rogan D. Immune parameters in mares resistant and susceptible to persistent post-breeding endometritis: Effects of immunomodulation. Vet Immunol Immunopathol. 2007;118:30–9.
71. Marey MA, Liu J, Kowsar R, Haneda S, Matsui M, Sasaki M, et al. Bovine oviduct epithelial cells downregulate phagocytosis of sperm by neutrophils: Prostaglandin E2 as a major physiological regulator. Reproduction. 2014;147:211–9.
72. Rodriguez-Martinez H, Nicander L, Viring S, Einarsson S, Larsson K. Ultrastructure of the uterotubal junction in preovulatory pigs. Anat Histol Embryol. 1990;19:16–36.
73. Yousef MS, Marey MA, Hambruch N, Hayakawa H, Shimizu T, Hussien HA, et al. Sperm Binding to Oviduct Epithelial Cells Enhances TGFB1 and IL10 Expressions in Epithelial Cells as Well as Neutrophils In Vitro: Prostaglandin E2 As a Main Regulator of Anti-Inflammatory Response in the Bovine Oviduct. PLoS One. 2016;11:e0162309.
74. Fazeli A, Affara NA, Hubank M, Holt W V. Sperm-induced modification of the oviductal gene expression profile after natural insemination in mice. Biol Reprod. 2004;71:60–5.
75. Georgiou AS, Snijders APL, Sostaric E, Aflatoonian R, Vazquez JL, Vazquez JM, et al. Modulation of the oviductal environment by gametes. J Proteome Res. 2007;6:4656–66.
76. Artemenko K, Horáková J, Steinberger B, Besenfelder U, Brem G, Bergquist J, et al. A proteomic approach to monitor the dynamic response of the female oviductal epithelial cell surface to male gametes. J Proteomics. 2015;113:1–14.
77. Ignotz GG, Cho MY, Suarez SS. Annexins are candidate oviductal receptors for bovine sperm surface proteins and thus may serve to hold bovine sperm in the oviductal reservoir. Biol Reprod. 2007;77:906–13.
78. Gwathmey TM, Ignotz GG, Suarez SS. PDC-109 (BSP-A1/A2) promotes bull sperm binding to oviductal epithelium in vitro and may be involved in forming the oviductal sperm reservoir. Biol Reprod. 2003;69:809–15.
79. Gwathmey TM, Ignotz GG, Mueller JL, Manjunath P, Suarez SS. Bovine seminal plasma proteins PDC-109, BSP-A3, and BSP-30-kDa share functional roles in storing sperm in the oviduct. Biol Reprod. 2006;75:501–7.
80. Yudin AI, Tollner TL, Li M-W, Treece CA, Overstreet JW, Cherr GN. ESP13.2, a member of the beta-defensin family, is a macaque sperm surface-coating protein involved in the capacitation process. Biol Reprod. 2003;69:1118–28.
81. Ezz MA, Marey MA, Elweza AE, Kawai T, Heppelmann M, Pfarrer C, et al. TLR2/4 signaling pathway mediates sperm-induced inflammation in bovine endometrial epithelial cells in vitro. PLoS One. 2019;14:e0214516.
82. Suarez SS, Brockman K, Lefebvre R. Distribution of mucus and sperm in bovine oviducts after artificial insemination: the physical environment of the oviductal sperm reservoir. Biol Reprod. 1997;56:447–53.
83. Suarez SS. Formation of a Reservoir of Sperm in the Oviduct. Reprod Domest Anim. 2002;37:140–3.
84. Hunter RH. Significance of the epithelial crypts at the bovine utero-tubal junction in the pre-ovulatory phase of sperm regulation. Acta Vet Scand. 1995;36:413–21.
85. Muro Y, Hasuwa H, Isotani A, Miyata H, Yamagata K, Ikawa M, et al. Behavior of Mouse Spermatozoa in the Female Reproductive Tract from Soon after Mating to the Beginning of Fertilization. Biol Reprod. 2016;94:80.
86. Parrish JJ, Susko-Parrish J, Winer MA, First NL. Capacitation of bovine sperm by heparin. Biol Reprod. 1988;38:1171–80.
87. Wijayagunawardane MP, Miyamoto A, Cerbito WA, Acosta TJ, Takagi M, Sato K. Local distributions of oviductal estradiol, progesterone, prostaglandins, oxytocin and endothelin-1 in the cyclic cow. Theriogenology. 1998;49:607–18.
88. Borges ÁM, Healey GD, Sheldon IM. Explants of Intact Endometrium to Model Bovine Innate Immunity and Inflammation Ex Vivo. Am J Reprod Immunol. 2012;67:526–39.
89. Denissenko P, Kantsler V, Smith DJ, Kirkman-Brown J. Human spermatozoa migration in microchannels reveals boundary-following navigation. Proc Natl Acad Sci. 2012;109:8007–10.
90. Tung CK, Hu L, Fiore AG, Ardon F, Hickman DG, Gilbert RO, et al. Microgrooves and fluid flows provide preferential passageways for sperm over pathogen Tritrichomonas foetus. Proc Natl Acad Sci U S A. 2015;112:5431–6.
91. Ralt D, Manor M, Cohen-Dayag A, Tur-Kaspa I, Ben-Shlomo I, Makler A, et al. Chemotaxis and chemokinesis of human spermatozoa to follicular factors. Biol Reprod. 1994;50:774–85.
92. Dickmann Z. Chemotaxis of rabbit spermatozoa. J Exp Biol. 1963;40:1–5.
93. Schwartz R, Brooks W, Zinsser HH. Evidence of chemotaxis as a factor in sperm motility. Fertil Steril. 1958;9:300–8.
94. Fazleabas AT, Hild-Petito S, Verhage HG. Secretory proteins and growth factors of the baboon (Papio anubis) uterus: potential roles in pregnancy. Cell Biol Int. 1994;18:1145–53.
95. Allison Gray C, Bartol FF, Taylor KM, Wiley AA, Ramsey WS, Ott TL, et al. Ovine uterine gland knock-out model: effects of gland ablation on the estrous cycle. Biol Reprod. 2000;62:448–56.
96. Kane MT, Morgan PM, Coonan C. Peptide growth factors and preimplantation development. Hum Reprod Update. 1997;3:137–57.
97. Ashworth CJ, Bazer FW. Changes in Ovine Conceptus and Endometrial Function Following Asynchronus Embryo Transfer or Administration of Progesterone1. Biol Reprod. 1989;40:425–33.
98. Dutta S, Aoki K, Doungkamchan K, Tiemeyer M, Bovin N, Miller DJ. Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan. J Biol Chem. 2019;294:13445–63.
99. Fair T. The contribution of the maternal immune system to the establishment of pregnancy in cattle. Front Immunol. 2015;6 JAN:1–8.
100. Sheldon IM, Cronin JG, Bromfield JJ. Tolerance and Innate Immunity Shape the Development of Postpartum Uterine Disease and the Impact of Endometritis in Dairy Cattle. Annu Rev Anim Biosci. 2019;7:361–84.
101. Zralý Z, Čanderle J, Diblíková I, Švecová D, Mašková J, Kummer V. Antisperm antibodies in cows as related to their reproductive health. Acta Vet Brno. 2003;72:27–32.
102. Hong J, Dicker BL, Jayasinghe SN, De Gregorio F, Tian H, Han DY, et al. Strong inhibition of neutrophil-sperm interaction in cattle by selective phosphatidylinositol 3-kinase inhibitors. Biol Reprod. 2017;97:671–87.
103. Kodithuwakku SP, Miyamoto A, Wijayagunawardane MPB. Spermatozoa stimulate prostaglandin synthesis and secretion in bovine oviductal epithelial cells. Reproduction. 2007;133:1087–94.
104. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162:156–9.
105. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 2001;25:402–8.
106. Wahab M, Thompson J, Hamid B, Deen S, Al-Azzawi F. Endometrial histomorphometry of trimegestone-based sequential hormone replacement therapy: A weighted comparison with the endometrium of the natural cycle. Hum Reprod. 1999;14:2609–18.
107. De Winter PJJ, Verdonck M, De Kruif A, Coryn M, Deluyker HA, Devriese LA, et al. The relationship between the blood progesterone concentration at early metoestrus and uterine infection in the sow. Anim Reprod Sci. 1996;41:51–9.
108. Cohen J, Tyler KR. Sperm populations in the female genital tract of the rabbit. J Reprod Fertil. 1980;60:213–8.
109. Quayle A. The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells. J Reprod Immunol. 2002;57:61–79. Koga K, Mor G. Review Article: Expression and Function of Toll-Like Receptors at the Maternal—Fetal Interface. Reprod Sci. 2008;15:231–42.
110. Koga K, Mor G. Review Article: Expression and Function of Toll-Like Receptors at the Maternal—Fetal Interface. Reprod Sci. 2008;15:231–42.
111. Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197– 216.
112. Mogensen TH. Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses. Clin Microbiol Rev. 2009;22:240–73.
113. Davies D, Meade KG, Herath S, Eckersall PD, Gonzalez D, White JO, et al. Toll-like receptor and antimicrobial peptide expression in the bovine endometrium. Reprod Biol Endocrinol. 2008;6:53.
114. Sheldon IM, Cronin J, Goetze L, Donofrio G, Schuberth H-J. Defining Postpartum Uterine Disease and the Mechanisms of Infection and Immunity in the Female Reproductive Tract in Cattle1. Biol Reprod. 2009;81:1025–32.
115. Liu Z, Shimada M, Richards JS. The involvement of the Toll-like receptor family in ovulation. J Assist Reprod Genet. 2008;25:223–8.
116. Shimada M, Yanai Y, Okazaki T, Noma N, Kawashima I, Mori T, et al. Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization. Development. 2008;135:2001–11.
117. Cheng K, Wang X, Zhang S, Yin H. Discovery of small-molecule inhibitors of the TLR1/TLR2 complex. Angew Chemie - Int Ed. 2012;51:12246–9.
118. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, et al. Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4. J Exp Med. 2002;195:99–111.
119. Asea A, Rehli M, Kabingu E, Boch JA, Baré O, Auron PE, et al. Novel Signal Transduction Pathway Utilized by Extracellular HSP70. J Biol Chem. 2002;277:15028–34.
120. Park JS, Svetkauskaite D, He Q, Kim J-Y, Strassheim D, Ishizaka A, et al. Involvement of Toll-like Receptors 2 and 4 in Cellular Activation by High Mobility Group Box 1 Protein. J Biol Chem. 2004;279:7370–7.
121. Schaefer L, Babelova A, Kiss E, Hausser H-J, Baliova M, Krzyzankova M, et al. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J Clin Invest. 2005;115:2223–33.