Mannose-binding Lectin (MBL) as a susceptible host factor influencing Indian Visceral Leishmaniasis

Mishra, Anshuman; Antony, Justin S.; Gai, Prabhanjan P.; Sundaravadivel, Pandarisamy; Tong, Hoang Van; Jha, Aditya Nath; Singh, Lalji; Velavan, Thirumalaisamy P.; Thangaraj, Kumarasamy

doi:10.1016/j.parint.2015.08.003

Cited by 11 publications

(21 citation statements)

References 47 publications

(52 reference statements)

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“…Altogether, these results suggest that there is no influence of genotypes or serum MBL levels in the susceptibility to VL caused by L. chagasi in the studied population. These results differ from other studies in Brazil and other countries of Africa that report an association between polymorphism of the MBL 2 gene and leishmaniasis (Santos et al, 2001;Alonso et al, 2007;Asgharzadeh et al, 2007;Hamdi et al, 2013;Araujo et al, 2015;Mishra et al, 2015a). However, these associations are controversial, since genotypes conferring high production of MBL have already been associated with both susceptibility (Alonso et al, 2007;Asgharzadeh et al, 2007) and resistance (Araujo et al, 2015;Mishra et al, 2015a) to leishmaniasis.…”

Section: Diplotypescontrasting

confidence: 73%

“…Previous studies had shown that these polymorphisms can influence the occurrence of VL disease, but the results are inconsistent. A recent study with Indian population found no relationship between VL and variants at promoter sites −550H/L; −221X/Y, but the +4Q allele, which leads to high levels of MBL, was associated with relative protection against VL (Mishra et al, 2015a). Individuals with -221YY genotype, which leads to high levels of MBL, had a higher risk of developing VL caused by L. infantum in Moroccan population (Hamdi et al, 2013).…”

Section: Diplotypesmentioning

confidence: 92%

“…A study with Iran population has shown that, there is no difference between the haplotypes in patients with VL compared with healthy individuals (Asgharzadeh et al, 2007). However, two recent studies have shown a higher frequency of HYPA haplotype among healthy individuals, indicating its possible protective role against the leishmaniasis (Mishra et al, 2015a;Araujo et al, 2015). The HYPA haplotype has also been already associated with the protection against Schistossoma haematobium (Antony et al, 2013).…”

Section: Diplotypesmentioning

confidence: 99%

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Research Article Polymorphisms of the mannose binding lectin (<i>MBL2</i>) gene are related to protein plasma levels but not with visceral leishmaniasis in a northeastern brazilian population

Silva¹,

Pestaña²,

Monteiro³

et al. 2019

Genet. Mol. Res.

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Mannose-binding lectin (MBL) is a lectin complement protein encoded by the MBL2 gene that has an important role in the control of infections caused by intracellular pathogens. However, there is no consensus about the effect of MBL2 polymorphism and MBL levels in leishmaniasis infections. We investigated the implications of MBL2 gene variants as well as MBL serum levels and occurrence of visceral leishmaniosis (VL) caused by Leishmania chagasi. A case-control analytic study was performed on 161 patients with VL and 161 healthy individuals in a northeast region of Brazil. The alleles of exon 1 (MBL2*A, MBL2*B, MBL2*C and MBL2*D) and promoter region (-©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 18 (2): gmr18148 E.L. Silva et al. 2 550L/H,-221Y/X and +4P/Q) were identified by automatic sequencing and the MBL serum levels were determined using an ELISA kit. MBL serum levels were similar in VL patients compared to the healthy controls. Also, allelic, genotype and haplotype frequencies of variants in exon 1 and promoter region did not significantly differ between case and control groups. Overall, our data show that MBL2 polymorphisms within the structural gene as well as the promoter region influence functional MBL serum levels but are not associated with susceptibility to L. chagasi infection in this population. We observed a lack of consensus regarding the association of MBL 2 polymorphisms with leishmaniasis worldwide, indicating that the influence of genetic variations can differ in different populations and with differences in parasite/vector relationship.

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Section: Diplotypescontrasting

confidence: 73%

Section: Diplotypesmentioning

confidence: 92%

Section: Diplotypesmentioning

confidence: 99%

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Research Article Polymorphisms of the mannose binding lectin (<i>MBL2</i>) gene are related to protein plasma levels but not with visceral leishmaniasis in a northeastern brazilian population

Silva¹,

Pestaña²,

Monteiro³

et al. 2019

Genet. Mol. Res.

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“…It has been reported that serum exposure to the L. donovani ( 62 ), Leishmania major and Leishmania mexicana ( 63 ) promastigotes leads to activate the LP via binding of serum mannose-binding protein to the major surface glycoconjugates of the parasites and play important role in complement-mediated lysis. In contrary, the lysis of the parasites gets significantly reduced by the use of human serum depleted of lectin molecules MBL and ficolins ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Leishmania donovani Inhibitor of Serine Peptidases 2 Mediated Inhibition of Lectin Pathway and Upregulation of C5aR Signaling Promote Parasite Survival inside Host

et al. 2018

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Leishmania donovani, the causative agent of Indian visceral leishmaniasis has to face several barriers of the immune system inside the mammalian host for its survival. The complement system is one of the first barriers and consists of a well-balanced network of proteases including S1A family serine proteases (SPs). Inhibitor of serine peptidases (ISPs) is considered as inhibitor of S1A family serine peptidases and is reported to be present in trypanosomes, including Leishmania. In our previous study, we have deciphered the role of ISPs [LdISP1 and L. donovani inhibitor of serine peptidases 2 (LdISP2)] in the survival of L. donovani inside the sandfly midgut. However, the role of theses ISPs in the survival of L. donovani inside mammalian host still remains elusive. In the present study, we have deciphered the inhibitory effect of LdISPs on the host complement S1A serine peptidases, such as C1r/C1s and MASP1/MASP2. Our study suggested that although both rLdISP1 and rLdISP2 inferred strong interaction with C1complex and MBL-associated serine proteases (MASPs) but rLdISP2 showed the stronger inhibitory effect on MASP2 than rLdISP1. Moreover, we found that rLdISP2 significantly reduces the formation of C3, C5 convertase, and membrane attacking complex (MAC) by lectin pathway (LP) resulting in significant reduction in serum mediated lysis of the parasites. The role of LdISP2 on neutrophil elastase-mediated C5aR signaling was also evaluated. Notably, our results showed that infection of macrophages with ISP2-overexpressed Leishmania parasites significantly induces the expression of C5aR both at the transcript and translational level. Simultaneously, infection with ISP2KD parasites results in downregulation of host PI3K/AKT phosphorylation and increased in IL-12 production. Taken together, our findings clearly suggest that LdISP2 promotes parasite survival inside host by inhibiting MAC formation and complement-mediated lysis via LP and by upregulation of C5aR signaling.

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“…MBL was suggested as a candidate because (i) MBL binds to Leishmania (Green et al, 1994) (ii) it has been speculated whether some degree of positive selection for low MBL individuals exist since a high frequency of variant alleles causing lowered MBL levels are sustained in many populations – the hypothesis being that MBL mediates phagocytosis of pathogens able to reside inside phagocytes (Garred et al, 1994). Case-control studies of visceral leishmaniasis have concluded that the risk of infection is decreased in individuals with genotypes associated with low MBL levels (Alonso et al, 2007; Mishra et al, 2015), whereas a study of cutaneous leishmaniasis showed the opposite (Araujo et al, 2015). Increased MBL-driven macrophage uptake was not confirmed in the visceral leishmaniasis studies; hence, it is not clear if MBL acts as a direct opsonizer or if it mediates downstream C3b deposition ( Figure 1B (5)).…”

Section: Exploiting Lp Componentsmentioning

confidence: 99%

Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

et al. 2017

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The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination.

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Mannose-binding Lectin (MBL) as a susceptible host factor influencing Indian Visceral Leishmaniasis

Cited by 11 publications

References 47 publications

Research Article Polymorphisms of the mannose binding lectin (<i>MBL2</i>) gene are related to protein plasma levels but not with visceral leishmaniasis in a northeastern brazilian population

Research Article Polymorphisms of the mannose binding lectin (<i>MBL2</i>) gene are related to protein plasma levels but not with visceral leishmaniasis in a northeastern brazilian population

Leishmania donovani Inhibitor of Serine Peptidases 2 Mediated Inhibition of Lectin Pathway and Upregulation of C5aR Signaling Promote Parasite Survival inside Host

Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

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