SIGNR1-negative red pulp macrophages protect against acute streptococcal sepsis after Leishmania donovani-induced loss of marginal zone macrophages.

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.

Alveolar macrophages transport pathogens to lung draining lymph nodes.

The first step in inducing pulmonary adaptive immunity to allergens and airborne pathogens is Ag acquisition and transport to the lung draining lymph nodes (dLN). Dendritic cells (DC) sample the airways, and active transfer of Ag to the lung dLN is considered an exclusive property of migratory DC. However, alveolar macrophages (AM) are the first phagocytes to contact inhaled particulate matter.

c-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection.

Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or pneumococcal surface protein A (PspA) before pneumococcal challenge, were investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of Streptococcus pneumoniae either in vitro or in vivo.

Evidence for the involvement of lung-specific gammadelta T cell subsets in local responses to Streptococcus pneumoniae infection.

Although gammadelta T cells are involved in the response to many pathogens, the dynamics and heterogeneity of the local gammadelta T cell response remains poorly defined. We recently identified gammadelta T cells as regulators of macrophages and dendritic cells during the resolution of Streptococcus pneumoniae-mediated lung inflammation. Here, using PCR, spectratype analysis and flow cytometry, we show that multiple gammadelta T cell subsets, including those bearing Vgamma1, Vgamma4 and Vgamma6 TCR, increase in number in the lungs of infected mice, but not in associated lymphoid tissue.

CD11b regulates recruitment of alveolar macrophages but not pulmonary dendritic cells after pneumococcal challenge.

Despite their close physical and functional relationships, alveolar macrophages (AMs) and pulmonary dendritic cells (pulDCs) have rarely been examined together in the context of infection. Using a nonlethal, resolving model of pneumonia caused by intranasal injection of Streptococcus pneumoniae, we demonstrate that AMs and pulDCs exhibit distinct characteristics during pulmonary inflammation. Recruitment of AMs and pulDCs occurred with different kinetics, and increased numbers of AMs resulted mainly from the appearance of a distinct subset of CD11b(High) AMs.

Changes in soluble adhesion molecules in gingival crevicular fluid following periodontal surgery.

Background: Inflammation of periodontal tissues during postoperative wound healing is mediated by cell surface adhesion molecules. Soluble forms of these antigens have also been identified and shown to be important in immunoregulatory processes, but have previously not been investigated during periodontal repair and regeneration. The present study has examined the presence and possible changes in soluble intercellular adhesion molecule-1 (sICAM-1; CD54) and lymphocyte function-associated antigen-3 (sLFA-3; CD58) in gingival crevical fluid (GCF) following periodontal surgery.

The role played by tumor necrosis factor during localized and systemic infection with Streptococcus pneumoniae.

Tumor necrosis factor (TNF) has been proposed as a major mediator of host resistance in murine models of Streptococcus pneumoniae infection; in humans, anti-TNF therapies have been implicated in increased susceptibility to pneumococcal infection. Here, we use nonlethal (serotype 6B) and lethal (serotype 3) S. pneumoniae, neutralizing monoclonal antibodies to TNF, and TNF gene-deficient mice to reexamine the role played by TNF in antistreptococcal responses.

In vivo compartmentalization of functionally distinct, rapidly responsive antigen-specific T-cell populations in DNA-immunized or Salmonella enterica serovar Typhimurium-infected mice.

The location and functional properties of antigen-specific memory T-cell populations in lymphoid and nonlymphoid compartments following DNA immunization or infection with Salmonella were investigated. Epitope-specific CD8+ -T-cell expansion and retention during the memory phase were analyzed for DNA-immunized mice by use of a 5-h peptide restimulation assay. These data revealed that epitope-specific gamma interferon (IFN-gamma)-positive CD8+ T cells occur at higher frequencies in the spleen, liver, and blood than in draining or peripheral lymph nodes during the expansion phase.

Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responses.

CD8(+) T cells are essential for long-term, vaccine-induced resistance against intracellular pathogens. Here we show that natural antibodies, acting in concert with complement, are endogenous adjuvants for the generation of protective CD8(+) T cells after vaccination against visceral leishmaniasis. IL-4 was crucial for the priming of vaccine-specific CD8(+) T cells, and we defined the primary source of IL-4 as a CD11b(+)CD11c(lo) phagocyte.

The innate immune response differs in primary and secondary Salmonella infection.

This study examines innate immunity to oral Salmonella during primary infection and after secondary challenge of immune mice. Splenic NK and NKT cells plummeted early after primary infection, while neutrophils and macrophages (Mphi) increased 10- and 3-fold, respectively. In contrast, immune animals had only a modest reduction in NK cells, no loss of NKT cells, and a slight increase in phagocytes following secondary challenge.