Does T Helper Differentiation Correlate with Resistance or Susceptibility to Infection with L. major? Some Insights From the Murine Model

Abstract

The murine model of Leishmania major infection has been an invaluable tool in understanding T helper differentiation in vivo. The initial evidence for a role of distinct CD4+ T helper subsets in the outcome of infection was first obtained with this experimental model. The development of CD4+ Th1 cells was associated with resolution of the lesion, control of parasite replication, and resistance to re-infection in most of the mouse strains investigated (i.e., C57BL/6). In contrast, differentiation of CD4+ Th2 cells correlated with the development of unhealing lesions, and failure to control parasite load in a few strains (i.e., BALB/c). Since these first reports, an incredible amount of effort has been devoted to understanding the various parameters involved in the differentiation of these, and more recently discovered T helper subsets such as Th17 and T regulatory cells. The discovery of cross-talk between T helper subsets, as well as their plasticity force us to reevaluate the events driving a protective/deleterious T helper immune response following infection with L. major in mice. In this review, we describe the individual contributions of each of these CD4+ T helper subsets following L. major inoculation, emphasizing recent advances in the field, such as the impact of different substrains of L. major on the pathogenesis of disease.

Galectin-3 Facilitates Neutrophil Recruitment as an Innate Immune Response to a Parasitic Protozoa Cutaneous Infection

“…Several reports and the detailed analyses, however, indicate that the impact of neutrophils on leishmaniasis may vary depending on the substrains of L. major, in addition to the genetic background of mice (44,47). The studies to understand the possible exacerbating roles of neutrophils in leishmaniasis used one substrain of L. major (Friedlin) (41), although it remained unexplored whether such unexpected adverse function of neutrophils occurs with the infection with other substrains of L. major.…”

“…The acute depletion may induce unanticipated effects in the innate immunity because neutrophils constitute .50% of circulating leukocytes. Further, it has been recently noticed that there are some differences in the impact of different substrains of L. major on the pathogenesis of leishmaniasis (47). Thus, the biological significance of neutrophils in leishmaniasis deserves further studies that do not depend on the massive depletion of circulating neutrophils.…”

Role of Toll-Like Receptor 9 Signaling in Experimental Leishmania braziliensis Infection

“…Increasing evidence shows that the immune responses against distinct Leishmania species, and even within the same strains, can differ significantly (32). Given the role of TLR9 in resistance to other Leishmania infections, and the increased susceptibility seen in MyD88 Ϫ/Ϫ mice infected with L. braziliensis (33), we wanted to examine the role of TLR9 following L. braziliensis infection.…”

Timing is everything: dendritic cell subsets in murine Leishmania infection

“…A general consensus is that DCs at the site of infection take up parasites, acquire a mature phenotype and, upon migration to the dLN, present L. major antigens to CD4 + and CD8 + T cells via MHC-II and MHC-I respectively [39,40]. However, there is discord on the role of the different DC subsets due to differences in the parasite strains used (LV39, MHOM/IL/80/FE/BNI), the dosage (low dose or high dose), and the route of administration (subcutaneous or intra dermal) [41]. Many groups have identified the early presence of Leishmania antigen presenting dermal DCs (dDCs) moDC, followed by Langerhans cells, and finally, the dLN resident CD11b + cells themselves [42][43][44].…”