SIGNR1-Negative Red Pulp Macrophages Protect against Acute Streptococcal Sepsis after Leishmania donovani-Induced Loss of Marginal Zone Macrophages

A.C. Kirby, L. Beattie, A. Maroof, N. van Rooijen, P.M. Kaye

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Marginal zone macrophages in the murine spleen play an important role in the capture of blood-borne pathogens and are viewed as an essential component of host defense against the development of pneumococcal sepsis. However, we and others have previously described the loss of marginal zone macrophages associated with the splenomegaly that follows a variety of viral and protozoal infections; this finding raises the question of whether these infected mice would become more susceptible to secondary pneumococcal infection. Contrary to expectations, we found that mice lacking marginal zone macrophages resulting from Leishmania donovani infection have increased resistance to Streptococcus pneumoniae type 3 and do not develop sepsis. Using biophotonic imaging, we observed that pneumococci are rapidly trapped in the spleens of L donovani-infected mice. By selective depletion studies using clodronate liposomes, depleting monoclonal antibodies specific for Ly6C/G and Ly6G, and CD11c-DTR mice, we show that the enhanced early resistance in L. donovani-infected mice is entirely due to the activity of SIGNR1(-) red pulp macrophages. Our data demonstrate, therefore, that the normal requirement for SIGNR1(+) marginal zone macrophages to protect against a primary pneumococcal infection can, under conditions of splenomegaly, be readily compensated for by activated red pulp macrophages. (Am J Pathol 2009, 175:1107-1115; DOI: 10.2353/ajpath.2009.090258)
Original languageUndefined/Unknown
Pages (from-to)1107-1115
JournalThe American Journal of Pathology
Volume175
Issue number3
DOIs
Publication statusPublished - 2009

Cite this

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title = "SIGNR1-Negative Red Pulp Macrophages Protect against Acute Streptococcal Sepsis after Leishmania donovani-Induced Loss of Marginal Zone Macrophages",
abstract = "Marginal zone macrophages in the murine spleen play an important role in the capture of blood-borne pathogens and are viewed as an essential component of host defense against the development of pneumococcal sepsis. However, we and others have previously described the loss of marginal zone macrophages associated with the splenomegaly that follows a variety of viral and protozoal infections; this finding raises the question of whether these infected mice would become more susceptible to secondary pneumococcal infection. Contrary to expectations, we found that mice lacking marginal zone macrophages resulting from Leishmania donovani infection have increased resistance to Streptococcus pneumoniae type 3 and do not develop sepsis. Using biophotonic imaging, we observed that pneumococci are rapidly trapped in the spleens of L donovani-infected mice. By selective depletion studies using clodronate liposomes, depleting monoclonal antibodies specific for Ly6C/G and Ly6G, and CD11c-DTR mice, we show that the enhanced early resistance in L. donovani-infected mice is entirely due to the activity of SIGNR1(-) red pulp macrophages. Our data demonstrate, therefore, that the normal requirement for SIGNR1(+) marginal zone macrophages to protect against a primary pneumococcal infection can, under conditions of splenomegaly, be readily compensated for by activated red pulp macrophages. (Am J Pathol 2009, 175:1107-1115; DOI: 10.2353/ajpath.2009.090258)",
author = "A.C. Kirby and L. Beattie and A. Maroof and {van Rooijen}, N. and P.M. Kaye",
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SIGNR1-Negative Red Pulp Macrophages Protect against Acute Streptococcal Sepsis after Leishmania donovani-Induced Loss of Marginal Zone Macrophages. / Kirby, A.C.; Beattie, L.; Maroof, A.; van Rooijen, N.; Kaye, P.M.

In: The American Journal of Pathology, Vol. 175, No. 3, 2009, p. 1107-1115.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - SIGNR1-Negative Red Pulp Macrophages Protect against Acute Streptococcal Sepsis after Leishmania donovani-Induced Loss of Marginal Zone Macrophages

AU - Kirby, A.C.

AU - Beattie, L.

AU - Maroof, A.

AU - van Rooijen, N.

AU - Kaye, P.M.

PY - 2009

Y1 - 2009

N2 - Marginal zone macrophages in the murine spleen play an important role in the capture of blood-borne pathogens and are viewed as an essential component of host defense against the development of pneumococcal sepsis. However, we and others have previously described the loss of marginal zone macrophages associated with the splenomegaly that follows a variety of viral and protozoal infections; this finding raises the question of whether these infected mice would become more susceptible to secondary pneumococcal infection. Contrary to expectations, we found that mice lacking marginal zone macrophages resulting from Leishmania donovani infection have increased resistance to Streptococcus pneumoniae type 3 and do not develop sepsis. Using biophotonic imaging, we observed that pneumococci are rapidly trapped in the spleens of L donovani-infected mice. By selective depletion studies using clodronate liposomes, depleting monoclonal antibodies specific for Ly6C/G and Ly6G, and CD11c-DTR mice, we show that the enhanced early resistance in L. donovani-infected mice is entirely due to the activity of SIGNR1(-) red pulp macrophages. Our data demonstrate, therefore, that the normal requirement for SIGNR1(+) marginal zone macrophages to protect against a primary pneumococcal infection can, under conditions of splenomegaly, be readily compensated for by activated red pulp macrophages. (Am J Pathol 2009, 175:1107-1115; DOI: 10.2353/ajpath.2009.090258)

AB - Marginal zone macrophages in the murine spleen play an important role in the capture of blood-borne pathogens and are viewed as an essential component of host defense against the development of pneumococcal sepsis. However, we and others have previously described the loss of marginal zone macrophages associated with the splenomegaly that follows a variety of viral and protozoal infections; this finding raises the question of whether these infected mice would become more susceptible to secondary pneumococcal infection. Contrary to expectations, we found that mice lacking marginal zone macrophages resulting from Leishmania donovani infection have increased resistance to Streptococcus pneumoniae type 3 and do not develop sepsis. Using biophotonic imaging, we observed that pneumococci are rapidly trapped in the spleens of L donovani-infected mice. By selective depletion studies using clodronate liposomes, depleting monoclonal antibodies specific for Ly6C/G and Ly6G, and CD11c-DTR mice, we show that the enhanced early resistance in L. donovani-infected mice is entirely due to the activity of SIGNR1(-) red pulp macrophages. Our data demonstrate, therefore, that the normal requirement for SIGNR1(+) marginal zone macrophages to protect against a primary pneumococcal infection can, under conditions of splenomegaly, be readily compensated for by activated red pulp macrophages. (Am J Pathol 2009, 175:1107-1115; DOI: 10.2353/ajpath.2009.090258)

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