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B1 B lymphocytes play a critical role in host protection against lymphatic filarial parasites.

Paciorkowski N, Porte P, Shultz LD, Rajan TV - J. Exp. Med. (2000)

Bottom Line: These results suggest that B1 B cells are necessary to mediate host resistance to Brugian infection.Sterile clearance of the remaining parasite burden appears to require cell-mediated immunity.These data raise the possibility that the identification of molecule(s) recognized by humoral immune mechanisms might help generate prophylactic vaccines.

View Article: PubMed Central - PubMed

Affiliation: University of Connecticut Health Center, Farmington, Connecticut 06030-3105, USA.

ABSTRACT
Host defense against multicellular, extracellular pathogens such as nematode parasites is believed to be mediated largely, if not exclusively, by T lymphocytes. During our investigations into the course of Brugia malayi and Brugia pahangi infections in immunodeficient mouse models, we found that mice lacking B lymphocytes were permissive for Brugian infections, whereas immunocompetent mice were uniformly resistant. Mice bearing the Btk(xid) mutation were as permissive as those lacking all B cells, suggesting that the B1 subset may be responsible for host protection. Reconstitution of immunodeficient recombination activating gene (Rag)-1(-/)- mice with B1 B cells conferred resistance, even in the absence of conventional B2 lymphocytes and most T cells. These results suggest that B1 B cells are necessary to mediate host resistance to Brugian infection. Our data are consistent with a model wherein early resistance to B. malayi is mediated by humoral immune response, with a significant attrition of the incoming infectious larval load. Sterile clearance of the remaining parasite burden appears to require cell-mediated immunity. These data raise the possibility that the identification of molecule(s) recognized by humoral immune mechanisms might help generate prophylactic vaccines.

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Related in: MedlinePlus

Comparison of B. pahangi infection in C57BL/6J Igh6, Hfh11nu, and +/+ mice. Cohorts of age-matched B6 +/+, Hfh11nu, and Igh6 male mice received intraperitoneal injection of ∼50 B. pahangi L3. Batches of five mice of each group were necropsied at 1, 2, and 3 wk (w) after infection. Worm burdens were quantitated and expressed as a percentage of the infective dose (50). The bars represent average worm recoveries from five mice ±SD. White bars, B6 +/+; gray bars, B6 Hfh11nu; hatched bars, B6 Igh6 mice.
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Figure 1: Comparison of B. pahangi infection in C57BL/6J Igh6, Hfh11nu, and +/+ mice. Cohorts of age-matched B6 +/+, Hfh11nu, and Igh6 male mice received intraperitoneal injection of ∼50 B. pahangi L3. Batches of five mice of each group were necropsied at 1, 2, and 3 wk (w) after infection. Worm burdens were quantitated and expressed as a percentage of the infective dose (50). The bars represent average worm recoveries from five mice ±SD. White bars, B6 +/+; gray bars, B6 Hfh11nu; hatched bars, B6 Igh6 mice.

Mentions: In light of these findings, we reevaluated the role of T versus B lymphocytes in filarial infection using immunodeficient mice on the B6, CBA, and BALB/c backgrounds, which are all permissive for Brugian infections. Our studies revealed that mice homozygous for the induced Igh6 mutation, which causes a profound deficiency of B lymphocytes, are permissive to a level comparable to B6 SCID mice, which lack both B and T lymphocyte subsets 13. We repeated this experiment with the closely related filarial nematode, B. pahangi. The results are shown in Fig. 1. Mice that lack B cells fail to control B. pahangi infection, just as they are unable to contain B. malayi infection. In contrast, B cell–competent but T cell–deficient B6 NUDE animals demonstrate reduced worm burdens as early as 1 wk after infection. However, it is important to stress that the reduced worm burdens in these mice persist indefinitely, and the mice become patent and productive of microfilariae. Thus, B cell–competent T cell–deficient mice reduce worm burdens early in infection through a T cell–independent mechanism, but do not accomplish sterile immunity seen in fully immunocompetent +/+ mice.


B1 B lymphocytes play a critical role in host protection against lymphatic filarial parasites.

Paciorkowski N, Porte P, Shultz LD, Rajan TV - J. Exp. Med. (2000)

Comparison of B. pahangi infection in C57BL/6J Igh6, Hfh11nu, and +/+ mice. Cohorts of age-matched B6 +/+, Hfh11nu, and Igh6 male mice received intraperitoneal injection of ∼50 B. pahangi L3. Batches of five mice of each group were necropsied at 1, 2, and 3 wk (w) after infection. Worm burdens were quantitated and expressed as a percentage of the infective dose (50). The bars represent average worm recoveries from five mice ±SD. White bars, B6 +/+; gray bars, B6 Hfh11nu; hatched bars, B6 Igh6 mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195839&req=5

Figure 1: Comparison of B. pahangi infection in C57BL/6J Igh6, Hfh11nu, and +/+ mice. Cohorts of age-matched B6 +/+, Hfh11nu, and Igh6 male mice received intraperitoneal injection of ∼50 B. pahangi L3. Batches of five mice of each group were necropsied at 1, 2, and 3 wk (w) after infection. Worm burdens were quantitated and expressed as a percentage of the infective dose (50). The bars represent average worm recoveries from five mice ±SD. White bars, B6 +/+; gray bars, B6 Hfh11nu; hatched bars, B6 Igh6 mice.
Mentions: In light of these findings, we reevaluated the role of T versus B lymphocytes in filarial infection using immunodeficient mice on the B6, CBA, and BALB/c backgrounds, which are all permissive for Brugian infections. Our studies revealed that mice homozygous for the induced Igh6 mutation, which causes a profound deficiency of B lymphocytes, are permissive to a level comparable to B6 SCID mice, which lack both B and T lymphocyte subsets 13. We repeated this experiment with the closely related filarial nematode, B. pahangi. The results are shown in Fig. 1. Mice that lack B cells fail to control B. pahangi infection, just as they are unable to contain B. malayi infection. In contrast, B cell–competent but T cell–deficient B6 NUDE animals demonstrate reduced worm burdens as early as 1 wk after infection. However, it is important to stress that the reduced worm burdens in these mice persist indefinitely, and the mice become patent and productive of microfilariae. Thus, B cell–competent T cell–deficient mice reduce worm burdens early in infection through a T cell–independent mechanism, but do not accomplish sterile immunity seen in fully immunocompetent +/+ mice.

Bottom Line: These results suggest that B1 B cells are necessary to mediate host resistance to Brugian infection.Sterile clearance of the remaining parasite burden appears to require cell-mediated immunity.These data raise the possibility that the identification of molecule(s) recognized by humoral immune mechanisms might help generate prophylactic vaccines.

View Article: PubMed Central - PubMed

Affiliation: University of Connecticut Health Center, Farmington, Connecticut 06030-3105, USA.

ABSTRACT
Host defense against multicellular, extracellular pathogens such as nematode parasites is believed to be mediated largely, if not exclusively, by T lymphocytes. During our investigations into the course of Brugia malayi and Brugia pahangi infections in immunodeficient mouse models, we found that mice lacking B lymphocytes were permissive for Brugian infections, whereas immunocompetent mice were uniformly resistant. Mice bearing the Btk(xid) mutation were as permissive as those lacking all B cells, suggesting that the B1 subset may be responsible for host protection. Reconstitution of immunodeficient recombination activating gene (Rag)-1(-/)- mice with B1 B cells conferred resistance, even in the absence of conventional B2 lymphocytes and most T cells. These results suggest that B1 B cells are necessary to mediate host resistance to Brugian infection. Our data are consistent with a model wherein early resistance to B. malayi is mediated by humoral immune response, with a significant attrition of the incoming infectious larval load. Sterile clearance of the remaining parasite burden appears to require cell-mediated immunity. These data raise the possibility that the identification of molecule(s) recognized by humoral immune mechanisms might help generate prophylactic vaccines.

Show MeSH
Related in: MedlinePlus