The cellular niche of Listeria monocytogenes infection changes rapidly in the spleen

Abstract

The spleen is an important organ for the host response to systemic bacterial infections. Many cell types and cell surface receptors have been shown to play role in the capture and control of bacteria, yet these are often studied individually and a coherent picture has yet to emerge of how various phagocytes collaborate to control bacterial infection. We analyzed the cellular distribution of Listeria monocytogenes (LM) in situ during the early phase of infection. Using an immunohistochemistry approach, five distinct phagocyte populations contained LM after i.v. challenge and accounted for roughly all bacterial signal in tissue sections. Our analysis showed that LM was initially captured by a wide range of phagocytes in the marginal zone, where the growth of LM appeared to be controlled. The cellular distribution of LM within phagocyte populations changed rapidly during the first few hours, decreasing in marginal zone macrophages and transiently increasing in CD11c 1 DC. After 4-6 h LM was transported to the periarteriolar lymphoid sheath where the infective foci developed and LM grew exponentially.Key words: Bacterial infection . DC . Listeria monocytogenes . Macrophages . Spleen Supporting Information available online IntroductionThe spleen is an important site for host responses to bacterial infection [1,2]. Within the spleen, bacteria may encounter various tissue resident phagocytes including macrophages, DC, and neutrophils [3,4]. Marginal zone macrophages (MZM) are positioned along the outer layer of the marginal sinus where they have direct access to bacteria entering the spleen from the circulation. These macrophages express MARCO (macrophage receptor with collagenous structure), a type-1 scavenger receptor, related to the SR-A family of receptors [5], which recognizes bacterial cell-wall-associated polyanions [6]. MZM also express the C-type lectin, SIGN-R1. SIGN-R1 binds dextran [7] and facilitates the capture of polysaccharide antigens on bacteria such as Streptococcus pneumoniae [8]. A separate class of MZM, the metallophilic MZM (MMM), localize between the inner marginal sinus and the B-cell follicle [9]. These cells recognize sialic acid and LPS from Neiseria meningitidis [10] through Siglec-1 (sialicacid-binding-Ig-like-lectin 1) [11,12]. MMM have also been shown to produce interferon during Herpes simplex virus infection [13], but their role in bacterial infection is unclear, although it was reported that they produce CCL2 [14].Neutrophils play a crucial role in controlling bacterial infection [15][16][17][18][19]. They are present in the marginal zone (MZ) and Results LM enters a wide variety of phagocytes immediately after challengeWe found that the recovery of LM (EGD)-infected host cells from spleen was unreliable; $90% of LM CFU were lost in the process of isolating phagocytes and making single cell suspensions (Supporting Information Fig. 1). As an alternative, we developed an antibody staining approach, by which we identified five distinct phagocyte populations in spleen cryosections ( Fig....

Listeria monocytogenes engineered to activate the Nlrc4 inflammasome are severely attenuated and are poor inducers of protective immunity

“…Another possibility is that ΔactA/ΔinlB L. monocytogenes-L.p.FlaA kills antigen-presenting cells. Indeed, the majority of splenic L. monocytogenes are found within dendritic cells (DCs) rapidly after infection (36,37). However, we saw no significant difference in the total number of DCs or the number of dead DCs between ΔactA/ΔinlB L. monocytogenes-L.p.FlaA and the ΔactA/ΔinlB infections, with the exception being the slightly higher number of both total and dead DC in ΔactA/ΔinlB L. monocytogenes-L.p.FlaA-infected mice 24 h postinfection (Fig.…”

Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity againstListeria monocytogenes

“…Additionally, cytosolic localization of Lm is a prerequisite for TLR2-independent IL-12 and TNFα induction (31), as well as early IFNγ production from CD8 + T cells (20), highlighting the importance of NLRs for initiating cytokine production in this infection model. Finally, the redistribution of Lm within the microarchitecture of infected tissues such as the spleen (35,36) and the spatial and hierarchical coordination of cells and inflammatory cytokine production by DCs (37) suggest that the innate immune response and inflammatory cytokine production is more complex than the linear model of TLR-or NLR-signaling cascades within a single cell type.…”

Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist

“…5A), prompting us to focus on two types of macrophages known to be distributed on the LN surface, Siglec-1 + (also called CD169 or MOMA-1) macrophages (also known as subcapsular sinus macrophages) and MARCO + macrophages (31). Histological analysis using conventional fluorescence microscopy did not suitably reveal the entire iLN surface; moreover, these macrophages were difficult to isolate for flow cytometric analysis (32,33). Hence, we used two-photon microscopy imaging analysis to clarify the distribution of antigen and K3-SPG ex vivo.…”