The Protective Th1 Response in Mice is Induced in the T-cell Zone Only Three Weeks After Infection with Leishmania Major and Not During Early T-cell Activation

Overview

Journal Med Microbiol Immunol

Specialty Allergy & Immunology

Date 2011 May 7

PMID 21547563

Citations 8

Authors

Julia Barthelmann

Julia Nietsch

Maike Blessenohl

Tamas Laskay

Ger van Zandbergen

Jurgen Westermann

Kathrin Kalies

Affiliations

Soon will be listed here.

Abstract

The protozoan parasite Leishmania spp. causes clinical pictures ranging in severity from spontaneously healing skin ulcers to systemic disease. The immune response associated with healing involves the differentiation of IFNγ-producing Th1 cells, whereas the non-healing phenotype is associated with IL4-producing Th2 cells. The widespread assumption has been that the T-cell differentiation that leads to a healing or non-healing phenotype is established at the time of T-cell activation early after infection. By selectively analyzing the expression of cytokine genes in the T-cell zones of lymph nodes of resistant (Th1) C57BL/6 mice and susceptible (Th2) BALB/c mice during an infection with Leishmania major in vivo, we show that the early T-cell response does not differ between C57BL/6 mice and BALB/c mice. Instead, Th1/Th2 polarization appears suddenly 3 weeks after infection. At the same time point, the number of parasites increases in lymph nodes of both mouse strains, but about 100-fold more in susceptible BALB/c mice. We conclude that the protective Th1 response in C57BL/6 mice is facilitated by the capacity of their innate effector cells to keep parasite numbers at low levels.

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References

Sacks D, Noben-Trauth N . The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol. 2002; 2(11):845-58. DOI: 10.1038/nri933. View

Leon B, Lopez-Bravo M, Ardavin C . Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. Immunity. 2007; 26(4):519-31. DOI: 10.1016/j.immuni.2007.01.017. View

Colpitts S, Scott P . The early generation of a heterogeneous CD4+ T cell response to Leishmania major. J Immunol. 2010; 185(4):2416-23. PMC: 2944829. DOI: 10.4049/jimmunol.1000483. View

Baldwin T, Henri S, Curtis J, OKeeffe M, Vremec D, Shortman K . Dendritic cell populations in Leishmania major-infected skin and draining lymph nodes. Infect Immun. 2004; 72(4):1991-2001. PMC: 375196. DOI: 10.1128/IAI.72.4.1991-2001.2004. View

Moll H, Rollinghoff M . Resistance to murine cutaneous leishmaniasis is mediated by TH1 cells, but disease-promoting CD4+ cells are different from TH2 cells. Eur J Immunol. 1990; 20(9):2067-74. DOI: 10.1002/eji.1830200927. View

Roth A, Konig P, van Zandbergen G, Klinger M, Hellwig-Burgel T, Daubener W . Hypoxia abrogates antichlamydial properties of IFN-γ in human fallopian tube cells in vitro and ex vivo. Proc Natl Acad Sci U S A. 2010; 107(45):19502-7. PMC: 2984208. DOI: 10.1073/pnas.1008178107. View

Smith K, Brewer J, Mowat A, Ron Y, Garside P . The influence of follicular migration on T-cell differentiation. Immunology. 2004; 111(3):248-51. PMC: 1782427. DOI: 10.1111/j.1365-2567.2004.01813.x. View

Lagrange P, Mackaness G, Miller T . Influence of dose and route of antigen injection on the immunological induction of T cells. J Exp Med. 1974; 139(3):528-42. PMC: 2139541. DOI: 10.1084/jem.139.3.528. View

Carrera L, Gazzinelli R, Badolato R, Hieny S, Muller W, Kuhn R . Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice. J Exp Med. 1996; 183(2):515-26. PMC: 2192469. DOI: 10.1084/jem.183.2.515. View

10.

Junt T, Scandella E, Ludewig B . Form follows function: lymphoid tissue microarchitecture in antimicrobial immune defence. Nat Rev Immunol. 2008; 8(10):764-75. DOI: 10.1038/nri2414. View

11.

Laskay T, Diefenbach A, Rollinghoff M, Solbach W . Early parasite containment is decisive for resistance to Leishmania major infection. Eur J Immunol. 1995; 25(8):2220-7. DOI: 10.1002/eji.1830250816. View

12.

Santarem N, Silvestre R, Tavares J, Silva M, Cabral S, Maciel J . Immune response regulation by leishmania secreted and nonsecreted antigens. J Biomed Biotechnol. 2007; 2007(6):85154. PMC: 1940321. DOI: 10.1155/2007/85154. View

13.

Scott P, Artis D, Uzonna J, Zaph C . The development of effector and memory T cells in cutaneous leishmaniasis: the implications for vaccine development. Immunol Rev. 2004; 201:318-38. DOI: 10.1111/j.0105-2896.2004.00198.x. View

14.

van Zandbergen G, Bollinger A, Wenzel A, Kamhawi S, Voll R, Klinger M . Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum. Proc Natl Acad Sci U S A. 2006; 103(37):13837-42. PMC: 1564231. DOI: 10.1073/pnas.0600843103. View

15.

Reiner S, Zheng S, Wang Z, Stowring L, Locksley R . Leishmania promastigotes evade interleukin 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD4+ T cells during initiation of infection. J Exp Med. 1994; 179(2):447-56. PMC: 2191353. DOI: 10.1084/jem.179.2.447. View

16.

Sadick M, Heinzel F, Holaday B, Pu R, Dawkins R, Locksley R . Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. J Exp Med. 1990; 171(1):115-27. PMC: 2187647. DOI: 10.1084/jem.171.1.115. View

17.

Nicolas L, Prina E, Lang T, Milon G . Real-time PCR for detection and quantitation of leishmania in mouse tissues. J Clin Microbiol. 2002; 40(5):1666-9. PMC: 130941. DOI: 10.1128/JCM.40.5.1666-1669.2002. View

18.

Scott P, Eaton A, Gause W, di Zhou X, Hondowicz B . Early IL-4 production does not predict susceptibility to Leishmania major. Exp Parasitol. 1996; 84(2):178-87. DOI: 10.1006/expr.1996.0103. View

19.

Zhang X, Brunner T, Carter L, Dutton R, Rogers P, Bradley L . Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis. J Exp Med. 1997; 185(10):1837-49. PMC: 2196321. DOI: 10.1084/jem.185.10.1837. View

20.

Mosmann T, Cherwinski H, Bond M, Giedlin M, Coffman R . Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986; 136(7):2348-57. View