HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bliss, S. K. Articles by Denkers, E. Y. Search for Related Content PubMed PubMed Citation Articles by Bliss, S. K. Articles by Denkers, E. Y.

Murine Neutrophil Stimulation by Toxoplasma gondii Antigen Drives High Level Production of IFN--Independent IL-12¹

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

Successful immunity to Toxoplasma gondii requires a strong cell-mediated immune response. Neutrophils possess the ability to rapidly migrate into tissues in response to microbial stimuli. Therefore, we sought to determine whether murine neutrophils could respond to T. gondii by producing immunoregulatory cytokines. We show that murine neutrophils produce high levels of IL-12 and low, but significant, levels of TNF- when stimulated with T. gondii Ag. Both cytokines are produced in the absence of IFN-. Production of IL-12 does not require TNFR p55, and release of TNF- occurs independently of IL-12. We show that there is an influx of neutrophils into the peritoneal cavity that peaks at 8 h in response to injection of live tachyzoites and that this is correlated with increased transcription of IL-12 p40. Our results establish that murine neutrophils possess the ability to produce immunoregulatory cytokines during T. gondii infection and suggest that this response may be important in early host defense and in triggering cell-mediated immunity to the parasite.

This article has been cited by other articles:

				A. M. Pollard, S. Skariah, D. G. Mordue, and L. J. Knoll A Transmembrane Domain-Containing Surface Protein from Toxoplasma gondii Augments Replication in Activated Immune Cells and Establishment of a Chronic Infection Infect. Immun., September 1, 2009; 77(9): 3731 - 3739. [Abstract] [Full Text] [PDF]

				J. P. Gigley, B. A. Fox, and D. J. Bzik Cell-Mediated Immunity to Toxoplasma gondii Develops Primarily by Local Th1 Host Immune Responses in the Absence of Parasite Replication J. Immunol., January 15, 2009; 182(2): 1069 - 1078. [Abstract] [Full Text] [PDF]

				W. Sukhumavasi, C. E. Egan, A. L. Warren, G. A. Taylor, B. A. Fox, D. J. Bzik, and E. Y. Denkers TLR Adaptor MyD88 Is Essential for Pathogen Control during Oral Toxoplasma gondii Infection but Not Adaptive Immunity Induced by a Vaccine Strain of the Parasite J. Immunol., September 1, 2008; 181(5): 3464 - 3473. [Abstract] [Full Text] [PDF]

				W. Sukhumavasi, C. E. Egan, and E. Y. Denkers Mouse Neutrophils Require JNK2 MAPK for Toxoplasma gondii-Induced IL-12p40 and CCL2/MCP-1 Release J. Immunol., September 15, 2007; 179(6): 3570 - 3577. [Abstract] [Full Text] [PDF]

				K. V. Sawant and D. N. McMurray Guinea Pig Neutrophils Infected with Mycobacterium tuberculosis Produce Cytokines Which Activate Alveolar Macrophages in Noncontact Cultures Infect. Immun., April 1, 2007; 75(4): 1870 - 1877. [Abstract] [Full Text] [PDF]

				H. Li, Z. Gang, H. Yuling, X. Luokun, X. Jie, L. Hao, W. Li, H. Chunsong, L. Junyan, J. Mingshen, et al. Different Neurotropic Pathogens Elicit Neurotoxic CCR9- or Neurosupportive CXCR3-Expressing Microglia J. Immunol., September 15, 2006; 177(6): 3644 - 3656. [Abstract] [Full Text] [PDF]

				S. Bennouna, W. Sukhumavasi, and E. Y. Denkers Toxoplasma gondii Inhibits Toll-Like Receptor 4 Ligand-Induced Mobilization of Intracellular Tumor Necrosis Factor Alpha to the Surface of Mouse Peritoneal Neutrophils Infect. Immun., July 1, 2006; 74(7): 4274 - 4281. [Abstract] [Full Text] [PDF]

				C.-H. Liu, Y.-t. Fan, A. Dias, L. Esper, R. A. Corn, A. Bafica, F. S. Machado, and J. Aliberti Cutting Edge: Dendritic Cells Are Essential for In Vivo IL-12 Production and Development of Resistance against Toxoplasma gondii Infection in Mice J. Immunol., July 1, 2006; 177(1): 31 - 35. [Abstract] [Full Text] [PDF]

				C. W. Lee, S. Bennouna, and E. Y. Denkers Screening for Toxoplasma gondii-Regulated Transcriptional Responses in Lipopolysaccharide-Activated Macrophages Infect. Immun., March 1, 2006; 74(3): 1916 - 1923. [Abstract] [Full Text] [PDF]

				P. M. Robben, M. LaRegina, W. A. Kuziel, and L. D. Sibley Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis J. Exp. Med., June 6, 2005; 201(11): 1761 - 1769. [Abstract] [Full Text] [PDF]

				S. Bennouna and E. Y. Denkers Microbial Antigen Triggers Rapid Mobilization of TNF-{alpha} to the Surface of Mouse Neutrophils Transforming Them into Inducers of High-Level Dendritic Cell TNF-{alpha} Production J. Immunol., April 15, 2005; 174(8): 4845 - 4851. [Abstract] [Full Text] [PDF]

				E. B. Eruslanov, I. V. Lyadova, T. K. Kondratieva, K. B. Majorov, I. V. Scheglov, M. O. Orlova, and A. S. Apt Neutrophil Responses to Mycobacterium tuberculosis Infection in Genetically Susceptible and Resistant Mice Infect. Immun., March 1, 2005; 73(3): 1744 - 1753. [Abstract] [Full Text] [PDF]

				D. P. Beiting, S. K. Bliss, D. H. Schlafer, V. L. Roberts, and J. A. Appleton Interleukin-10 Limits Local and Body Cavity Inflammation during Infection with Muscle-Stage Trichinella spiralis Infect. Immun., June 1, 2004; 72(6): 3129 - 3137. [Abstract] [Full Text] [PDF]

				L. Del Rio, B. A. Butcher, S. Bennouna, S. Hieny, A. Sher, and E. Y. Denkers Toxoplasma gondii Triggers Myeloid Differentiation Factor 88-Dependent IL-12 and Chemokine Ligand 2 (Monocyte Chemoattractant Protein 1) Responses Using Distinct Parasite Molecules and Host Receptors J. Immunol., June 1, 2004; 172(11): 6954 - 6960. [Abstract] [Full Text] [PDF]

				P. M. Robben, D. G. Mordue, S. M. Truscott, K. Takeda, S. Akira, and L. D. Sibley Production of IL-12 by Macrophages Infected with Toxoplasma gondii Depends on the Parasite Genotype J. Immunol., March 15, 2004; 172(6): 3686 - 3694. [Abstract] [Full Text] [PDF]

				L. C. Gavrilescu, B. A. Butcher, L. Del Rio, G. A. Taylor, and E. Y. Denkers STAT1 Is Essential for Antimicrobial Effector Function but Dispensable for Gamma Interferon Production during Toxoplasma gondii Infection Infect. Immun., March 1, 2004; 72(3): 1257 - 1264. [Abstract] [Full Text] [PDF]

				D. G. Mordue and L. D. Sibley A novel population of Gr-1+-activated macrophages induced during acute toxoplasmosis J. Leukoc. Biol., December 1, 2003; 74(6): 1015 - 1025. [Abstract] [Full Text]

				S. Bennouna, S. K. Bliss, T. J. Curiel, and E. Y. Denkers Cross-Talk in the Innate Immune System: Neutrophils Instruct Recruitment and Activation of Dendritic Cells during Microbial Infection J. Immunol., December 1, 2003; 171(11): 6052 - 6058. [Abstract] [Full Text] [PDF]

				M. Emoto, M. Miyamoto, Y. Emoto, I. Yoshizawa, V. Brinkmann, N. van Rooijen, and S. H. E. Kaufmann Highly Biased Type 1 Immune Responses in Mice Deficient in LFA-1 in Listeria monocytogenes Infection Are Caused by Elevated IL-12 Production by Granulocytes J. Immunol., October 15, 2003; 171(8): 3970 - 3976. [Abstract] [Full Text] [PDF]

				S. K. Bliss, A. Alcaraz, and J. A. Appleton IL-10 Prevents Liver Necrosis During Murine Infection with Trichinella spiralis J. Immunol., September 15, 2003; 171(6): 3142 - 3147. [Abstract] [Full Text] [PDF]

				A. C. Kirby, U. Yrlid, and M. J. Wick The Innate Immune Response Differs in Primary and Secondary Salmonella Infection J. Immunol., October 15, 2002; 169(8): 4450 - 4459. [Abstract] [Full Text] [PDF]

				M. J. Lyons, T. Yoshimura, and D. N. McMurray Mycobacterium bovis BCG Vaccination Augments Interleukin-8 mRNA Expression and Protein Production in Guinea Pig Alveolar Macrophages Infected with Mycobacterium tuberculosis Infect. Immun., October 1, 2002; 70(10): 5471 - 5478. [Abstract] [Full Text] [PDF]

				B. A. Butcher and E. Y. Denkers Mechanism of Entry Determines the Ability of Toxoplasma gondii To Inhibit Macrophage Proinflammatory Cytokine Production Infect. Immun., September 1, 2002; 70(9): 5216 - 5224. [Abstract] [Full Text] [PDF]

				C. A. Scanga, J. Aliberti, D. Jankovic, F. Tilloy, S. Bennouna, E. Y. Denkers, R. Medzhitov, and A. Sher Cutting Edge: MyD88 Is Required for Resistance to Toxoplasma gondii Infection and Regulates Parasite-Induced IL-12 Production by Dendritic Cells J. Immunol., June 15, 2002; 168(12): 5997 - 6001. [Abstract] [Full Text] [PDF]

				A. S. MacDonald, E. A. Patton, A. C. La Flamme, M. I. Araujo, C. R. Huxtable, B. Bauman, and E. J. Pearce Impaired Th2 Development and Increased Mortality During Schistosoma mansoni Infection in the Absence of CD40/CD154 Interaction J. Immunol., May 1, 2002; 168(9): 4643 - 4649. [Abstract] [Full Text] [PDF]

				N. Mason, J. Aliberti, J. C. Caamano, H.-C. Liou, and C. A. Hunter Cutting Edge: Identification of c-Rel-Dependent and -Independent Pathways of IL-12 Production During Infectious and Inflammatory Stimuli J. Immunol., March 15, 2002; 168(6): 2590 - 2594. [Abstract] [Full Text] [PDF]

				M. Dalod, T. P. Salazar-Mather, L. Malmgaard, C. Lewis, C. Asselin-Paturel, F. Briere, G. Trinchieri, and C. A. Biron Interferon {alpha}/{beta} and Interleukin 12 Responses to Viral Infections: Pathways Regulating Dendritic Cell Cytokine Expression In Vivo J. Exp. Med., February 19, 2002; 195(4): 517 - 528. [Abstract] [Full Text] [PDF]

				N. M. Silva, C. V. Rodrigues, M. M. Santoro, L. F. L. Reis, J. I. Alvarez-Leite, and R. T. Gazzinelli Expression of Indoleamine 2,3-Dioxygenase, Tryptophan Degradation, and Kynurenine Formation during In Vivo Infection with Toxoplasma gondii: Induction by Endogenous Gamma Interferon and Requirement of Interferon Regulatory Factor 1 Infect. Immun., February 1, 2002; 70(2): 859 - 868. [Abstract] [Full Text] [PDF]

				L. Del Rio, S. Bennouna, J. Salinas, and E. Y. Denkers CXCR2 Deficiency Confers Impaired Neutrophil Recruitment and Increased Susceptibility During Toxoplasma gondii Infection J. Immunol., December 1, 2001; 167(11): 6503 - 6509. [Abstract] [Full Text] [PDF]

				B. A. Butcher, L. Kim, P. F. Johnson, and E. Y. Denkers Toxoplasma gondii Tachyzoites Inhibit Proinflammatory Cytokine Induction in Infected Macrophages by Preventing Nuclear Translocation of the Transcription Factor NF-{kappa}B J. Immunol., August 15, 2001; 167(4): 2193 - 2201. [Abstract] [Full Text] [PDF]

				S. K. Bliss, L. C. Gavrilescu, A. Alcaraz, and E. Y. Denkers Neutrophil Depletion during Toxoplasma gondii Infection Leads to Impaired Immunity and Lethal Systemic Pathology Infect. Immun., August 1, 2001; 69(8): 4898 - 4905. [Abstract] [Full Text] [PDF]

				L. C. Gavrilescu and E. Y. Denkers IFN-{{gamma}} Overproduction and High Level Apoptosis Are Associated with High but Not Low Virulence Toxoplasma gondii Infection J. Immunol., July 15, 2001; 167(2): 902 - 909. [Abstract] [Full Text] [PDF]

				K. Tateda, T. A. Moore, M. W. Newstead, W. C. Tsai, X. Zeng, J. C. Deng, G. Chen, R. Reddy, K. Yamaguchi, and T. J. Standiford Chemokine-Dependent Neutrophil Recruitment in a Murine Model of Legionella Pneumonia: Potential Role of Neutrophils as Immunoregulatory Cells Infect. Immun., April 1, 2001; 69(4): 2017 - 2024. [Abstract] [Full Text] [PDF]

				M. I. Araujo, S. K. Bliss, Y. Suzuki, A. Alcaraz, E. Y. Denkers, and E. J. Pearce Interleukin-12 Promotes Pathologic Liver Changes and Death in Mice Coinfected with Schistosoma mansoni and Toxoplasma gondii Infect. Immun., March 1, 2001; 69(3): 1454 - 1462. [Abstract] [Full Text] [PDF]

				K. Tateda, T. A. Moore, J. C. Deng, M. W. Newstead, X. Zeng, A. Matsukawa, M. S. Swanson, K. Yamaguchi, and T. J. Standiford Early Recruitment of Neutrophils Determines Subsequent T1/T2 Host Responses in a Murine Model of Legionella pneumophila Pneumonia J. Immunol., March 1, 2001; 166(5): 3355 - 3361. [Abstract] [Full Text] [PDF]

				I. A. Khan, P. M. Murphy, L. Casciotti, J. D. Schwartzman, J. Collins, J.-L. Gao, and G. R. Yeaman Mice Lacking the Chemokine Receptor CCR1 Show Increased Susceptibility to Toxoplasma gondii Infection J. Immunol., February 1, 2001; 166(3): 1930 - 1937. [Abstract] [Full Text] [PDF]

				S. K. Bliss, B. A. Butcher, and E. Y. Denkers Rapid Recruitment of Neutrophils Containing Prestored IL-12 During Microbial Infection J. Immunol., October 15, 2000; 165(8): 4515 - 4521. [Abstract] [Full Text] [PDF]

				J. Pedrosa, B. M. Saunders, R. Appelberg, I. M. Orme, M. T. Silva, and A. M. Cooper Neutrophils Play a Protective Nonphagocytic Role in Systemic Mycobacterium tuberculosis Infection of Mice Infect. Immun., February 1, 2000; 68(2): 577 - 583. [Abstract] [Full Text] [PDF]