SUMMARY Neutrophils are typically the first responders in host defense against invading pathogens, which they destroy by both oxidative and nonoxidative mechanisms. However, despite a longstanding recognition of neutrophil presence at disease sites in tuberculosis, their role in defense against mycobacteria is unclear. Here we exploit the genetic tractability and optical transparency of zebrafish to monitor neutrophil behavior and its consequences during infection with Mycobacterium marinum, a natural fish pathogen. In contrast to macrophages, neutrophils do not interact with mycobacteria at initial infection sites. Neutrophils are subsequently recruited to the nascent granuloma in response to signals from dying infected macrophages within the granuloma, which they phagocytose. Some neutrophils then rapidly kill the internalized mycobacteria through NADPH oxidase-dependent mechanisms. Our results provide a mechanistic link to the observed patterns of neutrophils in human tuberculous granulomas and the susceptibility of humans with chronic granulomatous disease to mycobacterial infection.

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Legionella pneumophila is the causative agent of Legionnaires’ disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC), which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

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In this paper, hydroxyapatite (HA) particles was modified with long-chain organic silane-Octadecyltrichlorosilane (OTS), and the modified particles were further used for preparing Poly(L-lactic acid) PLLA/HA porous composite. The modified particles were characterized by means of XRD, FTIR, and XPS techniques. Both XPS and FTIR results showed that OTS had been combined with HA, and the formation of P-O-Si bond, a covalent bond, on the HA particle surface was confirmed by XPS. OTS-modified HA particles were used to prepare porous composites by thermally induced phase separation method. The results showed that the composite had an interconnected pore structure with 100-300 mum macropores. With OTS dosage increasing during modification, the mechanical properties of PLLA/OTS-modified HA porous composites increased obviously. These results showed that OTS modification can effectively improve the interface compatibility between HA surface and PLLA.

In this work, Arg-Gly-Asp (RGD) sequence containing peptide was immobilized on hydroxyapatite (HA) coatings through a chemical bonding approach in two steps, surface modification with 3-aminopropyltriethoxysilane (APTES) and RGD immobilization. The results indicate that RGD has been successfully immobilized on HA coatings. Comparing with physical adsorption coatings, the chemically bonded RGD on the coatings shows much better anti-wash-out ability. Since RGD is able to recognize cell-membrane integrins on biointerfaces, the present method will be an effective way to favor interaction of cells with HA coatings.

causes Legionnaires' disease, a severe and potentially fatal bacterial pneumonia in immunocompromised individuals. Despite the understanding that a robust inflammatory response is important for control of infection, our understanding of the network of molecular and cellular events within the lung that function to clear the bacterium is not clearly understood. This review compiles our understanding of the various molecular and cellular pathways stimulated upon infection with and considers recently published advances that focus on the immune response to in the lungs of mice. This includes a cooperative network of tissue-resident and inflammatory phagocytes, including alveolar macrophages (AM)s, neutrophils, and inflammatory monocytes/monocyte-derived cells (MC) that contribute to the acute inflammatory response and restrict the bacteria via distinct intracellular pathways. The understanding of this difference in cellular activity in response to infection provides insight into the innate immune responses within the tissues in general and may prompt novel means of clinical management of bacterial infections in an era of increasing emergence of antibiotic resistance.