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Salazar Laboratory


Lyme Disease/Borrelia Burgdorferi

Cervantes, JL, La Vake, CJ, Weinerman, B, Luu, S, O'Connell, C, Verardi, PH, Salazar, JC. Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes. J. Leuk. Biol. 2013; 94:1-11. http://www.ncbi.nlm.nih.gov/pubmed/23906644.

Syphilis/Treponema Pallidum

Silver AC, Dunne DW, Zeiss CJ, Bockenstedt LK, Radolf JD, Salazar JC, and Fikrig. MyD88 deficiency markedly worsens tissue inflammation and bacterial clearance in mice infected with Treponema pallidum, the agent of syphilis. PLoS One 2013;  8: e71388. http://www.ncbi.nlm.nih.gov/pubmed/23940747.

Latest Research Related Publications (Peer Reviewed and Book Chapters)

Lomotey CL, Lewis J, Gebrian B, Bourdeau R, Dickhaus K, Salazar JC. Maternal and Congenital Syphilis in Rural Haiti. Pan Am J Public Health 2009; 26(3), 197-202.

Olson CM, Bates TC, Izadi H, Radolf JD, Huber SA, Boyson JE, Anguita J. Local production of interferon gamma by invariant natural killer cells modulates acute Lyme carditis. J Immunol 182 2009; 182:3728-3733.

Mulay VB, Caimano MJ, Iyer R, Ems S, Liveris D, Petzke MM, Schwartz I, and Radolf JD*. Borrelia burgdorferi bba74 is expressed exclusively during tick feeding and is regulated by both arthropod- and mammalian host-specific signals. J Bacteriol 2009; 191:2783-2794.

Dunham-Ems S, Caimano MJ, Pal U, Wolgemuth CW, Eggers CH, Balic A, and Radolf JD*. Live imaging reveals a novel, biphasic mode of dissemination of Borrelia burgdorferi within ticks. J Clin Invest 2009; 119:3652-3665.

Izard J, Renken C, Hsieh C-E, Desrosiers DC, Dunham-Ems S, La Vake C, Gebhardt LL, Limberger RJ, Cox DL, Marko M, and Radolf JD*. Cryo-electron tomography elucidates the molecular architecture of Treponema pallidum, the syphilis spirochete. J Bacteriol 2009; 191:7566-7580.

Sahay B, Patsey RL, Eggers CH, Salazar JC, Radolf JD, and Sellati TJ. CD14 signaling restrains chronic inflammation through induction of p38-MAPK/SOCS-dependent tolerance. PLOS Pathogens 2009; 5:e1000687.

Feder Jr. HM and Salazar JC. A clinical review of 105 patients with PFAPA (A periodic fever syndrome). Acta Pediatrica, 2009, September.

Sahay B, Patsey RL, Eggers CH, Salazar JC, Radolf JD, Sellati TJ. CD14 signaling restrains chronic inflammation through induction of p38-MAPK/SOCS-dependent tolerance. PLoS Pathog. 2009 Dec;5(12):e1000687.

Parsonage D, Desrosiers DC, Hazlett KRO, Sun Y, Nelson KJ, Cox DL, Radolf JD and Poole LB. Broad specificity AhpC-like peroxiredoxin and its thioredoxin reductant in the sparse antioxidant defense system of Treponama pallidum. Proc. Natl. Acad. Sci 2010; 107:6240-6245.

Earnhart CG, LeBlanc DV, Alix KE, Desrosiers DC, Radolf JD, and Marconi RT. Identification of residues within ligand binding domain 1 (LBD1) of the B. burgdorferi OspC protein required for function in the mammalian environment. Mol Microbiol 2010; 76:393-408.

Girotto JE. Etravirine: A unique non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1. Formulary. 2010;45:78–83; 101–103.

Salazar JC and Feder HM, Periodic Fever Syndromes. Chapter 176, in Textbook of Pediatric Dermatology, 3rd Edition, Edited by A. Irvine, P. Hoeger and A. Yan, 2010, Blackwell Publishing Ltd.

Courter JD, Baker WL, Nowak KS, Smogowicz LA, Desjardins LL, Coleman CI, Girotto JE. Increased clinical failures when treating acute otitis media with macrolides: a meta-analysis. Ann Pharmacother. 2010 Mar;44(3):471-8. Epub 2010 Feb 11.

Salazar JC. Management of an HIV-positive pregnant woman with a positive VDRL test from an area endemic for Treponema infection. Cohen and Powderly/Infectious Diseases 3e/Practice Point 23, Elsevier, to be published in March 2010.

Radolf JD, Salazar JC, and Dattwyler RJ, Lyme Disease in Humans, in Borrelia; Molecular Biology, Host Interaction and Pathogenesis. Edited by: D. Scott Samuels and Justin D. Radolf. Caister Academic Press, UK, to be published March 2010.

Courter JD; Girotto JE, Lobato MN, Orcutt D; Burke M, Feder HM; Krause PJ, Cohen-Abbo A; Salazar JC. Intravenous streptomycin treatment for an infant with tuberculosis meningitis. Accepted for publication in Pharmacotherapy, March, 2010.

Cruz AR, Pillay A, et al. Salazar JC. Secondary syphilis in Cali, Colombia: New concepts in disease pathogenesis. Accepted for publication in PLoS NTD, March 2010.

Johnson PN, Miller JL, Boucher EA, Lubsch L, Girotto JE, Pesaturo KA, Lee B, on behalf of the PPAG Advocacy Committee. Medication Dosing in Overweight and Obese Children. Pediatric Pharmacy Advocacy Group Position Statement. March 2010. Available at: http://www.ppag.org/obesedose/.

John M, Feder, HM. Chronic Lyme disease: a survey of Connecticut primary care physicians. J Pediatr 2010 published online 9/2/2010.

Deville JG, Goldfarb J, Kaplan SL, Equils O, Huang DB, Ang JY, Salazar JC. The use of linezolid in the treatment of paediatric patients with infections caused by enterococci including strains resistant to vancomycin. J Antimicrob Chemother. 2010 Oct;65(10):2267-70. Epub 2010 Aug 12. PubMed PMID: 20705627.

Desrosiers DC, Bearden SW, Mier I Jr, Abney J, Paulley JT, Fetherston JD, Salazar JC, Radolf JD, Perry RD. Znu is the predominant zinc importer in Yersinia pestis during in vitro growth but is not essential for virulence. Infect Immun. 2010 Sep 20. [Epub ahead of print] PubMed PMID: 20855510.

Cox DL, Luthra A, Dunham-Ems S, Desrosiers DC, Salazar JC, Caimano MJ, Radolf JD. Surface immunolabeling and consensus computational framework to identify candidate rare outer membrane proteins of Treponema pallidum. Infect Immun. 2010 Sep 27. [Epub ahead of print] PubMed PMID: 20876295.

Phung OJ, Coleman CI, Baker EL, Scholle JM, Girotto JE, Makanji SS, Chen WT, Talati R, Kluger J, White CM. Recombinant human growth hormone in the treatment of patients with cystic fibrosis. Pediatrics. 2010 Nov;126(5):e1211-26. Epub 2010 Oct 4.

Courter JD, Teevan CJ, Li MH, Girotto JE, Salazar JC. Role of tipranavir in treatment of patients with multidrug-resistant HIV. Ther Clin Risk Manag. 2010 Oct 5;6:431-41.

Courter JD, Girotto JE, Lobato MN, Orcutt D, Burke M, Feder HM Jr, Krause PJ, Cohen-Abbo A, Salazar JC. Intravenous streptomycin treatment for an infant with Mycobacterium tuberculosis meningitis. Pharmacotherapy 2010 Nov:30: 481e–484e.

Borrelia: Molecular Biology, Host Interaction and Pathogenesis. D Scott Samuels and JD Radolf, eds. Horizon Scientific Press, Norwich, UK.

Cervantes JL, Dunham-Ems SM, La Vake CJ, Petzke MM, Sahay B, Sellati TJ, Radolf JD, Salazar JC. Phagosomal signaling by Borrelia burgdorferi in human monocytes involves Toll-like receptor (TLR) 2 and TLR8 cooperativity and TLR8-mediated induction of IFN-β. Proc Natl Acad Sci. 2011 Mar 1;108(9):3683-8. Epub 2011 Feb 14.

Recent f1000 Review of Dr. Salazar's PNAS Publication


This study establishes a critical role for human Toll-like receptor 8 (TLR8) in bacterial sensing by monocytes. In this work, the authors build on their previous publication showing the important contribution of phagocytosis to the innate immune response against Borrelia burgdorferi (Bb) by monocytes {1}. Using a clever strategy of inhibiting TLR8 sensing by oligonucleotides, the authors establish that TLR2 and TLR8 cooperate in the immune response mounted against Bb.

Surface TLR2 was initially activated by live bacteria, which presumably increased phagocytosis of Bb — as shown with Listeria monocytogenes {2}. Subsequently, TLR2 and TLR8 were found to colocalize with degraded Bb in phagosomal vacuoles. Most importantly, this work demonstrates that TLR8 activation contributed to the induction of nuclear factor-kappaB (NFkB)-dependent cytokines promoted by TLR2, and was critical for the induction of interferon-beta (IFN-beta) through IFN regulatory factor 7 (IRF7) by phagocytosed Bb.

This work establishes further the key role of TLR8 in bacterial sensing, previously proposed for Mycobacterium tuberculosis/bovis and Helicobacter pylori {3,4}. Type-I IFN induction by TLR8 is likely to be a critical component of the monocytic response against other bacteria, and could be at play in cell survival following phagocytosis. Given that several bacteria are able to persist in monocyte phagosomes, these findings highlight the need for a better characterisation of the role of TLR8 in the immune response against phagosomal bacteria. It could be speculated that strategies modulating TLR8 sensing could offer novel therapeutic avenues to finely tune immune responses against phagocytosed bacteria.

View more publications, see Pubmed listing.