Immunobiology of Infections - Research Topics


 

The main areas of our investigation:

We reported associations of low serum MBL and ficolin-2 concentrations (and/or corresponding genotypes) with recurrence of paediatric respiratory infections (Cedzyński et al., 2004; Atkinson et al., 2004). Further investigation revealed that low ficolin-2 is rather associated with combined infectious and allergic respiratory disease (Cedzyński et al., 2009).

 

Low cord serum levels of MBL and ficolin-2 were associated with neonatal sepsis (Świerzko et al., 2016) and neonatal infections in general (Świerzko et al., 2009). Furthermore, low ficolin-2, ficolin-3 and MASP-2 were associated with premature births (Świerzko et al. 2009; Michalski et al., 2012). We reported the large series of MBL2 (six polymorphic sites)/serum MBL and FCN2 (seven polymorphic sites)/serum ficolin-2 genotype/phenotype relationships (Świerzko et al., 2009; Kilpatrick et al., 2013). Currently, we are investigating the role of genetically-determined and epigenetically-regulated ficolin-2 insufficiency in the susceptibility of preterm newborns to infections.

 

Over the years, several cases of rare MASP-2 and ficolin-3 primary deficiencies were presented and discussed. Two MASP-2 deficient individuals were found among children with recurrent respiratory infections (Cedzyński et al., 2004; 2009), two were adult pulmonary tuberculosis patients (Sokołowska et al., 2015) while one was 29-year old healthy volunteer (Sokołowska et al., 2015). One of described ficolin-3 deficient individuals was premature newborn, with perinatal severe infection, microcephaly, growth and mental retardation.  ADHD was diagnosed as well. However, no severe infection during 8-year follow-up was noted (Michalski et al., 2012; 2015). Another case affected 11-month old infant with congenital heart disease. He had post-operative pneumonia (with no recurrence); but no severe infections during several months follow-up. Ficolin-3 deficiency was found also in adult patient with membranous nephropathy and severe nephrotic syndrome. EBV infection but no other severe or recurrent infections was noted (Michalski et al., 2015).

 

We demonstrated that high preoperative MBL serum concentration may contribute to the development of sterile SIRS in children undergoing cardiac surgery. On the other hand, MBL deficiency was found to be a risk factor for postoperative infections (Pągowska-Klimek et al., 2016). We proven that cardiopulmonary bypass (CPB) induces activation of the complement cascade via the lectin pathway and demonstrated (in vitro) deposition of MBL and ficolins on the surface of  polyurethane tubings used for CPB (Eppa et al., 2018). We have found also that low serum ficolin-3 concentration (determined in pre-operatively taken samples) often was associatd with post-operative development of SIRS. On the other hand, in patients who developed SIRS, low ficolin-3 (<12,7 µg/ml) was associated with better prognosis while higher values – with higher risk for fatal outcome (Michalski et al., 2019).

 

High levels of MBL, ficolin-2 and ficolin-3 were associated with ovarian cancer. MBL deficiency-associated genotypes predicted prolonged survival in patients. Furthermore, altered local (ovarian) expression of MBL2, FCN2, FCN3 and MASP2 genes was found (Świerzko et al., 2007; 2014; Szala et al., 2013). It was found that recombinant ficolin-3 recognizes cells of some cancerous lines (the most effective binding to cells of ovarian cancer line) (Michalski et al., 2019). Moreover, we demonstrated high affinity of recombinant ficolin-3 to sections of ovarian malignant tumours (Michalski et al., 2019). In contrast, serum ficolin-3 occured to be not effective (also no effect is observed after supplementing normal serum with recombinant protein). That suggests presence of (unidentified to date) natural inhibitor, preventing binding of serum ficolin-3 to eukaryotic cells (Michalski et al., 2019).

During investigation concerning associations of collectins, ficolins and MASPs with haematological malignancies, we demonstrated that primary MBL deficiency may be associated with multiple myeloma (Świerzko et al., 2018). It is not associated with hospital infections or post-autologous haematopoietic stem cells transplantation (auto-HSCT) recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up (Świerzko et al., 2018). We found that MBL2 gene 3′-untranslated region polymorphisms may be associated with cancer (lymphoma). The possible disease association of MBL2 3’-UTR SNP were demonstrated for the first time in Caucasians (Świerzko et al., 2018). Furthermore, we found that high MBL and MASP-2 serum concentrations before chemotherapy are risk fators for hospital infections in patients (Świerzko et al., 2018).


Ficolin-3 was reported to recognize Hafnia alvei PCM1200 cells. The target for PRM was O-specific polysaccharide of bacterial lipopolysaccharide (LPS). That interaction resulted in complement activation (Świerzko et al., 2012). Later, ficolin-3-LPS interaction was shown to promote phagocytosis of bacteria (Michalski et al., 2015). H. alvei LPS was proposed to be useful for purification of ficolin-3 from plasma and determination of its concentration in body fluids (Świerzko et al., 2012; Michalski et al., 2012; Man-Kupisińska et al., 2016).

We demonstrated that MBL recognizes various slow-growing mycobacteria (Mycobacterium tuberculosis, M. bovis, M. kansasii, M. gordonae) as well as non-pathogenic M. smegmatis. Recognition resulted in activation of the lectin pathway of complement and an enhancement of phagocytosis. Furthermore we reported Interaction of ficolin-3 with M. tuberculosis, M. bovis and M. kansasii, and ficolin-1 with M. tuberculosis and M. bovis (Bartłomiejczyk et al., 2014). The mycobacterial Ag85 complex was identified as a target for human ficolins (Świerzko et al., 2016).

Thanks to investigation of reactivity of MBL with variety of Yersinia enterocolitica mutants,  we proposed mannoheptose residues located in the inner core oligosaccharide part of atypical Yersinia LPS as a target for MBL (Kasperkiewicz et al., 2015). Recently, we further investigated mechanisms of reactivity of MBL with LPS of other Enterobacteriaceae. Although the lectin is able to recognize numerous endotoxins via inner core oligosaccharide-located ligands, the ability to induce anaphylactoid shock is not common. However, LPS of some Hafnia alvei strains contain MBL targets (mannoheptose, Kdo) in outer core oligosaccharide are potent inducers of that reaction (Man-Kupisińska et al., 2018). That was in agreement with our previous (cited above) data concerning Proteus vulgaris O25 LPS (Świerzko et al., 2003).

 

Scientific collaboration:

International:

We collaborate with leading scientists and teams working on complement lectin pathway, for example:

Investigation of Yersinia LPS are conducted thanks to cooperation with University of Helsinki (Finland).

 

Domestic:

We collaborate with excellent physicians and scientists representing: