Cartilage oligomeric matrix protein was isolated in the native state from the Swarm rat chondrosarcoma. A crucial step was its selective extraction with EDTA-containing buffer. The purified protein was subjected to electron microscopy using rotary shadowing and negative stain. The images allowed the construction of a structural model. The bouquet-like protein consists of five 28-nm-long arms containing a peripheral globular domain, a flexible strand, and a central assembly domain, where the five arms meet in a cylindrical structure.

Immune checkpoint therapy, where CD8 tumor infiltrating T lymphocytes (TIL) are reactivated, is a promising anti‐cancer treatment approach, yet with low response rates. The extracellular matrix, in particular tenascin‐C, may generate barriers for TIL. To investigate this possibility, we used a MMTV‐NeuNT and syngeneic mammary gland grafting model derived thereof with engineered tenascin‐C levels and observed accumulation of CD8 TIL in tenascin‐C‐rich stroma. Inhibition studies revealed that tenascin‐C induced CXCL12 through TLR4. By binding CXCL12, tenascin‐C retained CD8 TIL in the stroma. Blockade of CXCR4, the receptor of CXCL12, enhanced macrophage and CD8 TIL infiltration and reduced tumor growth and subsequent metastasis. Retention of CD8 TIL by tenascin‐C/CXCL12 was also observed in human breast cancer by tissue staining. Moreover, whereas high CD8 TIL numbers correlated with longer metastasis‐free survival, this was not the case when also tenascin‐C and CXCL12 levels were high. Altogether, these results may be useful for improving tumor immunity as diagnostic tool and to formulate a future “TIL‐matrix‐release‐and‐reactivate” strategy.

Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the development of new drugs an urgent priority. In this study we have identified a promising candidate by screening antimicrobial peptides for their capacity to inhibit mycobacterial growth. This non-toxic peptide, NZX, is capable of inhibiting both clinical strains of M. tuberculosis and an MDR strain at therapeutic concentrations. The therapeutic potential of NZX is further supported in vivo where NZX significantly lowered the bacterial load with only five days of treatment, comparable to rifampicin treatment over the same period. NZX possesses intracellular inhibitory capacity and co-localizes with intracellular bacteria in infected murine lungs. In conclusion, the data presented strongly supports the therapeutic potential of NZX in future anti-TB treatment.

Gonorrhea is a sexually transmitted infection with 87 million new cases per year globally. Increasing antibiotic resistance has severely limited treatment options. A mechanism that Neisseria gonorrhoeae uses to evade complement attack is binding of the complement inhibitor C4b-binding protein (C4BP). We screened 107 porin B1a (PorB1a) and 83 PorB1b clinical isolates randomly selected from a Swedish strain collection over the last 10 years and noted that 96/107 (89.7%) PorB1a and 16/83 (19.3%) PorB1b bound C4BP; C4BP binding substantially correlated with the ability to evade complement-dependent killing ( r = 0.78). We designed 2 chimeric proteins that fused C4BP domains to the backbone of IgG or IgM (C4BP-IgG; C4BP-IgM) with the aim of enhancing complement activation and killing of gonococci. Both proteins bound gonococci ( K _D C4BP-IgM = 2.4 nM; K _D C4BP-IgG 980.7 nM), but only hexameric C4BP-IgM efficiently outcompeted heptameric C4BP from the bacterial surface, resulting in enhanced complement deposition and bacterial killing. Furthermore, C4BP-IgM substantially attenuated the duration and burden of colonization of 2 C4BP-binding gonococcal isolates but not a non–C4BP-binding strain in a mouse vaginal colonization model using human factor H/C4BP–transgenic mice. Our preclinical data present C4BP-IgM as an adjunct to conventional antimicrobials for the treatment of gonorrhea.

Equine recurrent uveitis (ERU) is considered one of the most important eye diseases in horses and typically appears with relapsing inflammatory episodes without systemic effects. Various disorders have been described as an initial trigger, including infections. Independent of the initiating cause, there are numerous indications that ERU is an immune-mediated disease. We investigated whether neutrophil extracellular traps (NETs) are part of the ERU pathogenesis. Therefore, vitreous body fluids (VBF), sera, and histological sections of the eye from ERU-diseased horses were analyzed for the presence of NET markers and compared with horses with healthy eyes. In addition, NET formation by blood derived neutrophils was investigated in the presence of VBF derived from horses with healthy eyes versus ERU-diseased horses using immunofluorescence microscopy. Interestingly, NET markers like free DNA, histone-complexes, and myeloperoxidase were detected in higher amounts in samples from ERU-diseased horses. Furthermore, in vitro NET formation was higher in neutrophils incubated with VBF from diseased horses compared with those animals with healthy eyes. Finally, we characterized the ability of equine cathelicidins to induce NETs, as potential NET inducing factors in ERU-diseased horses. In summary, our findings lead to the hypothesis that ERU-diseased horses develop more NETs and that these may contribute to the pathogenesis of ERU.